**FREQUENTLY ASKED QUESTIONS**

**NIH-NIAID-DAIDS-03-12**

**QUESTION** **1.** Note 5 to Offerors says that we must submit
agreement on collaboration IP and mechanism for resolving IP disputes
signed by all parties. We will not have this agreement for the final
receipt date as it needs to be negotiated by the commercial departments
of 2 Universities. We expect to have this sorted by the end of the
month. Will it be OK to have this signed agreement for then? If it would
help, I can get signed letters from both the Collaborators saying that
they are have seen the technical proposal and are willing to collaborate
on the sections as detailed.

**ANSWER** With respect this agreement it says very clearly in the RFP
(in bold letters) that "Proposals that do not include this agreement
will be returned to the Offeror without further review and will not be
considered for award." No extensions will be given to satisfy this
requirement. Furthermore these agreements must be signed by someone with
some administrative/business authority within the collaborating
institution (e.g. the signature of an academic co-PI is not sufficient
as such a person does not have the legal authority to assign a
university's patent rights).

**QUESTION 2.** There is no technical proposal page limits. Is that
correct?

**ANSWER** Yes, that is correct - no page limit.

**QUESTION 3.** We note that there has also been a program announcement
(PA) under NIAID\'s Integrated Preclinical/Clinical AIDS Vaccine
Development (IP/CAVD) funding mechanism, and are currently trying to
determine what the principal differences are between this and the above
RFP, and whether one is more appropriate . While we are currently
analyzing that PA to determine whether it or the HIV Vaccine Design &
Development Teams (HVDDT) RFP is more appropriate for our purposes, we
wondered if you could shed any light on how the aims of this IP/CAVD PA
differ from those of the HVDDT RFP?

**ANSWER** The IPCAVD PA is a mechanism for funding a multiproject
"Grant." This is an older Program that is in evolution. These Grants
usually combine 2 or 3 research projects linked to the central theme of
later stage development of a particular vaccine, plus 1 or 2 core units
that perform services for the research projects (one of these is usually
an "administrative" unit and the other may be a "central lab" or
"manufacturing" unit). As the name of this PA (Integrated
Preclinical/Clinical AIDS Vaccine Development) indicates the effort
should be linked to the purpose of getting a specific HIV/AIDS vaccine
concept from the lab into clinical trials; however, some of the research
projects have been very basic in nature. The HVDDT "Contracts" are more
unified product development efforts. They can include additional basic
research on developing further iterations of the vaccine, but they must
present a clear development path for getting a vaccine product into
clinical trials. The HVDDT Contract proposals are more carefully
reviewed for an understanding of all the necessary technical parts of
product development (e.g. GMP process development and manufacture,
preclinical toxicology, regulatory compliance) as well as the science
behind the basic concept. While both HVDDT Contractors and IP/CAVD
Grantees are required to get a product into clinical trials in the time
span of the Project neither are required to perform those trials under
the Contract or Grant budget; in fact they are both encouraged to apply
to the DAIDS HIV Vaccine Trials Network to perform the clinical trials
(and this can decrease their costs considerably and allow them to focus
their effort more).

Basically, these are two different funding mechanisms designed to do the
same thing - that is to get more AIDS vaccines into clinical trials. The
amount of money involved and the style of the projects/PIs may differ.
The HVDDT Contracts have been funded so far at a little bit more money
(about \$3-5M/year compared to about \$2M/year for IPCAVD grants) but
there is no actual limit on the funds someone can request under either
mechanism. The IPCAVDs have tended to include more basic research and,
as grants, they have less frequent reporting requirements both of which
the more academic type investigators like. But the IP/CAVDs have the
disadvantage getting less attention (and helpful advice) from DAIDS
Project Officers (there is actually a team of DAIDS project officers,
with backgrounds in nonhuman primatology, manufacturing, regulatory
compliance, and clinical trials, formed for each HVDDT Contract to track
progress and help with problems). The HVDDT Contracts are also required
to each have an External Advisory Board which reviews progress annually.
The HVDDT Contract mechanism was really designed to entice industry
types (and those academic types who understand the difference between
experiments and product development) into AIDS vaccine development; as
such they use a milestone-driven contract mechanism (with yearly
renegotiation of the milestone to both keep the goals reasonable and
keep the projects going as more of collaborations between DAIDS and
industry) which in our experience the more pragmatic industry types
serious about vaccine product development feel more comfortable with.

**QUESTION 4.** Do we need preclinical efficacy data prior to this
application?

**ANSWER** Demonstration of efficacy in a monkey model or demonstration
of the ability to induce cross-reactive neutralizing antibodies is not
required. However, the more your vaccine is based on a very novel
concept or an idea that is definitely not mainstream (in the academic
circles) the more helpful some evidence of efficacy from animal model
studies will be in the review process

**QUESTION 5.** Is a go/no-go decision point an acceptable milestone in
principle?  If the data support the no-go decision, does that preclude
cost reimbursement for the work leading up to that decision point? 

**ANSWER** A go/no-go decision point makes an excellent milestone. Even
if the decision is \"no-go\" you will get reimbursed for your costs and
fee. We are not going to penalize you for nature not being on your side.
 In good science good work does not always give you the results you are
hoping for, but if we want our Contractors to deliver us something that
works by doing good work and not glossing over problems then we have to
reward them for telling us the truth and making decisions appropriately
even when it is not the \"truth\" we had hoped for.

**QUESTION 6.** If significant budget commitments occur prior to
reaching a milestone that triggers cost reimbursement, and these exceed
a reasonable cash outflow for a small company offeror to sustain, are
there any mechanisms available to address cash flow constraints other
than redistributing into a more frequent series of milestones? 

**ANSWER** Invoicing has been monthly or quarterly, based on costs
expended, rather than linked to milestone accomplishment.  Fee payment
will be linked to milestone accomplishment; otherwise milestones are a
mechanism for Government technical oversight of the Contract as well as
continuous assessment of progress in the Contract for yearly NIAID
funding decisions. 

>  

**QUESTION 7.** The technology that will form the basis for our proposal
is also the subject of an existing HIVRAD grant. It is our intention
that our proposal will build on the output of that grant to develop
improved vaccine candidates for clinical evaluation, and that the HIVRAD
grant recipient will also be a collaborator/subcontractor for our
proposal, although on work that is not included in their HIVRAD program.
Are there other examples in which a single technology is a successful
offeror for multiple grants or contracts, and if not, is there any
difficulty with such a scenario if the programs are complementary? 

**ANSWER** It is very common for grant applicants and contract offerors
to use a single technology as the platform for development of several
different concepts or products or iterations of a single product. It is
also common for applicants/Offerors to apply at different times for
money to perform different aspects in the development of one product
(e.g.. basic research, GMP production, regulatory compliance studies).
This is acceptable as long as they do not request money to perform the
same specific work twice. We will compare proposals that get funded with
other grants/Contracts the Offeror may have for instances of
\"double-dipping\" and we will alter the budget appropriately; reviewers
will be informed of this so any possibly unfounded suspicions will not
impact review.

>  

**QUESTION 8.** The RFP (DAIDS-02-06) refers to 25-30,000 labor hours as
a guideline for project completion.  Our calculations suggest that this
is on the order of 2-3 full-time people.  Unless this is meant to refer
to dedicated full-time incremental project staff, this seems to
understate the typical resource necessary to fulfill the objectives of
the RFP, ie preclinical development and clinical evaluation of vaccine
candidates. 

**ANSWER** You are correct in thinking this number is too low.  This
estimate of labor hours was for the first year only in the cost estimate
submitted, not the full five years of the Contract.  We apologize for
not picking up the mistaken way it was put into the final RFP.

Successful Offerors in the first two HVDDT competitions submitted
budgets requesting between \$14M and \$24M over 5 years. These sums were
not evenly divided between the years of the Contracts, but rather varied
considerably from year to year depending upon the cost of the activities
to be performed.

**QUESTION 9.** The RFP refers to profit or fee as appropriate.  Does
this suggest that an offeror is entitled to earn fee\'s or profit over
and above program costs, or does it allude to the necessity that
commercial subcontractors will need to earn a profit on services or
materials that they supply? If the former, are there guidelines for what
is appropriate?

**ANSWER** The first interpretation is correct. Direct your attention to
\"Note 9 to Offeror\" where fees are discussed.

**QUESTION 10.** Is it necessary that all required technical resources
for the proposal be hired or in place in advance, or is it acceptable to
identify roles/positions that would be filled contingent on the contract
award? 

**ANSWER** The second is acceptable.  However, if subcontractors or key
personnel or facilities are not yet in place then the Offeror should
identify the criteria to be used in selecting them so that the reviewers
can judge the Offeror\'s competence.  And, obviously, if too many
positions and subcontractors are "TBN" this will reflect poorly on the
Proposal at review.

**QUESTION 11**. In the case of collaborators or subcontractors, how
complete or formal a commitment is required in advance? 

**ANSWER** In past competitions quotes from intended or competitive
subcontractors were acceptable; contracts did not have to be in place. 
The same should be acceptable this time.

**QUESTION 12.** In the context of process and product development, many
costs will be based on best estimates and will necessarily be based on
assumptions. How flexible is program management in terms of handling
ultimate required actual expenditure that exceeds original budget
estimates? We would like to propose our most reasonable expected costs,
but are anxious about having to absorb differences between estimates and
actual costs in areas like clinical trial materials, where the cost of
production is unavoidably uncertain at the time of submission.

**ANSWER** Most people are submitting estimates that take these
considerations into account and then actually under spending. For
unforeseen necessary costs that are within the scope of the contract
additional funding may be provided through a supplement to the contract.

**QUESTION 13.** In certain instances we may prefer to designate certain
external

contributions to the project as suppliers and in others as
subcontractors. Are there clear guidelines that specify these
designations? Can either also function as either paid or unpaid
consultants to the project outside their supplier or subcontractor
capacity?

**ANSWER** There are not clear guidelines on whether to designate
someone a supplier or a subcontractor. As to the second question there
is no reason why you can\'t pay someone as a consultant for advice in
addition to the actual work they perform as a subcontractor. (It is only
"double-dipping" if they collect twice for the same piece of work.)

**QUESTION 14.** We understand our travel cost estimates are to include
the costs of the scientific oversight committee and NIH staff periodic
review visits. Can you provide any input on standard assumptions you
wish offerors to use for this purpose?

**ANSWER** There are government, university and business standards for
travel; your organization may have already come to some agreement with
the Government if you have a Grant for research. The NIH budget pays for
the travel of NIH staff on review visits so you shouldn\'t budget for
that.

**QUESTION 15.** Regarding clinical studies (and in particular studies
run in the NIAID's HIV Vaccine Trials Network, the HVTN) do we need to
indicate the clinical investigators in the proposal and do we need to
list them as contractors or collaborators?

**ANSWER** You can say that you plan on performing clinical studies with
the HVTN and submit a letter of understanding or support from Larry
Corey (the PI of the HVTN) without listing HVTN investigators as
collaborators or contractors.

**QUESTION 16.** Can we run clinical studies outside the HVTN?

**ANSWER** You can run clinical studies outside the HVTN but then you
must either budget for them in your HVDDT budget or indicate that the
money for those trials will come from specific other sources. And you
should then pay very careful attention to how you will satisfy human
research subject protection concerns, as expressed by the DHHS OHRP, in
accordance with the norms and standards governing such studies performed
using U.S. Government funds.

**QUESTION 17**. If we plan to run SHIV monkey studies with the help of
the NIH SVEU (Simian Vaccine Evaluation Units), do they need to be
budgeted in the proposal?

**ANSWER** Monkey studies that the NIH SVEU has already approved should
be indicated in the proposal, but not budgeted for because they are
already being payed for by the NIH. It would probably be wise to request
money in your HVDDT budget for future as yet unapproved studies because
you can\'t be sure that all future requests to the NIH SVEU will be
granted.

**QUESTION 18**. Is there a recommended length of the technical part?

**ANSWER** Long enough to describe all the assays and technical
procedures, resources, etc. THOROUGHLY! It is not possible to be too
long - it is possible to be too short. Several past proposals were
considered non-responsive by the review panel because there was not
sufficient detail about the technical procedures to be employed
(including the key procedures of some key subcontractors).

Q**UESTION 19**. Do we need to produce GMP (and later on commercial)
clinical lots in the U.S.?

**ANSWER** You need to satisfy the FDA on this so that the product can
be tested at trial sites in the U.S. if that is your plan. The FDA
allows manufacture in inspected facilities in Europe. If you have any
question at all about the acceptability of your manufacturing facility
please consult the FDA.

**QUESTION 20.** Can we submit the proposal from our site outside the
U.S. or do we need to apply from within the U.S.?

**ANSWER** This RFP is open to International Offerors. You will neither
be penalized nor given any advantage at Review if you submit from a
foreign site.

**QUESTION 21**. What specific expenses will this grant (*sic*; *this is
not a "grant" -- it is a "Contract"*) fund to the company that can be
used to pay for each of: corporate salaries, overhead, employee
benefits, equipment for research/development/QC/QA, equipment for pilot
plant manufacture of product for Phase I and Phase II trials and any
other such corporate expenses?

**ANSWER** The Contract will pay for all of these things (although there
are some Government guidelines that cap salary reimbursement). A website
has been provided in the Instructions to Offerors indicating the Salary
Rate Limitation. This program was actually specifically designed to get
industry involved in the manufacture of candidate HIV/AIDS vaccines.
Your costs must be justified and the business proposal will be review
and selection will be based on a "best buy for the Government." Cost,
although not paramount, is a consideration in award.

**QUESTION 22.** With reference to note 6 to offeror: Can we support
manufacture of phase III product so that it would be ready for use in
trials? Can we support rennovation of facilities for GMP production of
product?

**ANSWER** It says very clearly in the RFP that this is not meant to
fund phase III trials. Of course when you are preparing your plasmid and
viral seed and working seed banks at the start of GMP manufacture for
Phase I you will put down enough to expand for phase III trials and that
can be paid for in this Contract, but the actual preparation and vialing
of the vaccine for the phase III trials should not be paid for with this
Contract (the material is liable to expire before a phase III trial
starts and that would be a waste). What we are seeking to do with this
funding mechanism, at this time, is to increase the number and diversity
of candidate HIV/AIDS vaccines in clinical trials; we are not yet at the
point of rewarding those most promising (at this time) candidates with
the funds to jump to the head of the queue for entering into a phase III
efficacy trial. We realize that everyone believes that their vaccine
candidate is the best (this is how it should be); however the AIDS
epidemic is so serious that the U.S. Government cannot afford to "put
all of its eggs in one basket" and not advance as many truly different
candidate vaccines as possible.

Contract money can be used to buy equipment, however, it is not normally
used for building or renovation.

**QUESTION 23.** Our team would like to know the importance the
government review committee would actually place on the value of a close
collaboration of a University research team with a vaccine manufacturing
company in this project. Are we correct in understanding that this kind
of \"research university and company\" collaboration is exactly what the
government is truly looking for and would give much more approval
consideration to that kind of partnership? That is, of course, assuming
that the technology is cutting edge and the company capable.

**ANSWER** You are completely correct in thinking that this mechanism
was designed to get university-industry partnerships working on HIV/AIDS
vaccines (the academics have the bright, innovative ideas needed because
the old ways of making vaccines haven\'t worked for AIDS, and industry
has the crucial expertise in product development, GMP manufacture and
regulatory compliance that is necessary to get a new vaccine into
clinical trials where we can find out whether it works).  However, your
question seems to specifically ask whether \"the review committee\" is
going to insist on seeing this (or give you extra credit).  The Review
panel will insist on a Proposal demonstrating a good idea that the
Offeror can really perform; this may not require a university-industry
partnership as long as all of the competencies are lined up. \[Note: One
of the successful Offerors in the first competition was a mostly
university consortium that had an industry add-on to ensure that the
industry portion was done right, while other Contracts went to Offerors
where the industry partner was the lead PI.\]  Any university group that
comes in alone, without any industry involvement (either as a co-PI or
an integral subcontractor) will probably not be successful, while some
large companies (with strong internal research programs) could be
successful without a university partner.

**QUESTION 24**. I noticed that under Note 5 in the \"Note To Offers\",
that the offeror must provide draft agreements signed by all parties
with their proposal. Traditionally, we have never had to provide signed
agreements to the NIH. As we are not yet guaranteed an award it appears
awkward to have agreements signed with potential collaborators if there
is a likelihood that the grant will not be awarded. Can you elaborate a
bit on the rationale for having these agreements in place?

**ANSWER** Note 5 states: \"The Offeror shall provide a draft agreement
signed by all parties involved outlining procedures to be used for: (1)
obtaining patent coverage and licensing of the resulting HIV vaccine,
and (2) procedures to be followed for the resolution of potential legal
issues that may arise. If this agreement is not included in the
Offeror's proposal, the proposal will be judged not acceptable. The
Offeror should also plan to obtain patent coverage and/or licensing for
all substances and technologies used in the vaccine product(s) made for
research and clinical trials.\"

These are very large (for the NIH) and complex Contracts usually
involving the collaboration of a group of individuals/companies. A
signed agreement of the sort that we ask is an indication of the
commitment, development, coherence, maturity, and management of the
group. You can write an agreement to just cover this Contract \"if it is
awarded\" and then you have no obligations or complications if you
don\'t get the contract. If you cannot come to agreement on how to deal
with intellectual property issues and resolve legal disputes among
yourselves before you start to work then that does not bode well for the
conduct of the Contract. In fact, in the first round of competition one
of the Proposals almost fell apart after they made the competitive range
cut and before the final selection because they couldn\'t come to terms
on patent issues; that group is now functioning very well - but without
one of the original co-PIs.

**QUESTION 25.** I have one question for you, since I am not familiar
with the way DAIDS handles these particular RFPs. If a proposal does not
meet the cut-off, is there an opportunity to re-submit it (after
addressing the reviewers comments), as in the case of an R01? 

**ANSWER** This is not a repeating RFP with regularly scheduled
application deadlines like R01, HIVRAD, or IP/CAVD grants.  But this is
the third competition for HVDDT Contracts, so Offerors who did not make
the cut in the past have the opportunity to reapply this time.  We do
not know at this time if another RFP like this will be issued (or if one
is issued when that will be).  All that can be said for sure about
future HVDDT RFPs is that there will not be another one for at least
another 12 months. 

**QUESTION 26.** We are a biotech company with more than 500 employees.
I noticed that several other large biotech companies, i.e. Chiron, have
received contracts from NIAID. Am I correct that we are eligible to
receive a contract under this RFP?

**ANSWER** This is not a small business set-aside (although small
businesses are encouraged to apply -- and have been successful Offerors
in past competition). Your company is eligible to receive one of these
awards.

**QUESTION 27.** At our company we are currently calculating average
costs per FTE for each specific R&D activity type (Bio-informatics,
Molecular Biology, Purification, fermentation, clinical
investigation\...) that we could split between direct costs & indirect
costs. We are also tracking and reporting the actuals the same way.
Would it be acceptable to the NIH if we submit a budget where we:

Provide an estimate of FTE for the project for each type of activity and
valuate them with the average cost per person. We wouldn\'t then provide
an actual estimation of materials consumption, or equipment used, or
actual travel of persons directly involved in the project. That would be
a direct function of the % FTE dedicated to the project. We are fully
prepared though to list all major materials, equipment that would
theoretically be used for the project and give you the cost/unit
currently negotiated with our suppliers as INFORMATION.

An example: cost/person in Purification department = 150,000 USD

> (: total costs of purif department/# of persons in purif department)
> we would split this between direct cost & indirect costs.

FTE estimated to work on HIV project for 2002 = 4.2

Then: Total costs for 2002 = 150,000 \*4.2

\+ List of price/unit of major materials, equipment used for
purification activities AS INFORMATION.

All identifiable external expenses such as lab analyses, investigators
fees will be clearly allocated to HIV project and tracked as such

Would that approach be acceptable to the NIH ?

**ANSWER** This is not like any of the budgets that came in for previous
competitions. The initial Review panel will not look at the budget
specifics (just a general breakdown, with which such a budget might be
made to appear consistent). However, the Source Selection Group, which
will evaluate the Proposals that made the competitive range after those
Offerors have answered technical questions asked by the Review panel,
will look at the budget in more detail and may not view such a budget
favorably.

**QUESTION 28.** I have a few questions on what needs to be filled in
for the section \"qualification of offeror\"

1- General experience: the overall experience of the company with
vaccine development? only HIV research?

2- Performance history & pertinents contracts: are we talking about any
R&D collaboration for any vaccine development or specifically
collaboration with NIH?

3- List of pertinant grants: only with NIH or other entities (EEC,
Path,\...)?

**ANSWER** This is an international competition; there are other
excellent Offerors. You should try to overwhelm the Reviewers with how
experienced and good you are, not just in HIV research, but also in
other areas of vaccine research. Not just collaboration with the NIH but
other collaborations on vaccine development. Of course you should
highlight the HIV work.

**QUESTION 29.** Do you want us to send quotes/documentation on
supplies/materials,

consultants, etc. with the initial submission of the contract proposal?
OR, IF it looks like we will get funded, then we produce the
documentation? OR, just keep the documentation on file in case we get
asked?

**ANSWER** You should send in as complete a budget as possible. Quotes
from potential subcontractors are sufficient. You shouldn\'t sign
contracts with subcontractors yet though because you don\'t know if you
will get the money from this competition, but you should find out how
much the work of the project will cost.

**QUESTION 30.** How many are on the External Advisory board, and would
\$1600 be an appropriate sum per board member?

**ANSWER** There should be about 5-6 people on your External Advisory
Board. You should budget to fly them into wherever the annual review
will take place, put them up at a hotel and feed them for 1-2 days for
each yearly meeting. The amount you should budget will depend on how far
they have to come and the hotel you select but \$1600 each sounds like
it is in the neighborhood of what the other Contracts are spending.

**QUESTION 31**. I am wondering how to deal with the Human Subjects
Evaluation section of the proposal. We plan to conduct clinical trials
through NIAID\'s HVTN in years 4-5 of the contract. Please let me know
what information is required in the proposal at this time.

**ANSWER** If you plan on having the DAIDS HVTN perform the clinical
studies then you, yourselves, will not actually be performing Human
Subject Research; and the HVTN and HVTN trial sites will meet all the
requirements of OHRP. The HVTN protocol development team will submit the
clinical protocol to our DAIDS Prevention Science Review Committee
(PSRC), our DAIDS Regulatory Affairs Branch would submit the IND
(Investigational New Drug) application to the FDA, the VTN trial
investigators would get the necessary local IRB (Institutional Review
Board) approvals from the local institutions where the clinical trials
will be performed, and the HVDDT Contractor would simply be making the
vaccine and submitting a Drug Master File to support the NIAID/HVTN\'s
IND. In this case the Contractor would be fulfilling their obligation to
Human Research Subject Protection through their submission of
information to the FDA and provision of information to the PSRC and the
Clinical Investigators in the \"Investigator\'s Brochure\" which they
will have to provide to the IND application. All of the training
required for doing clinical trials and the regulations governing those
trials will be satisfied by the HVTN sites. In the proposal the Offeror
should just make it very clear that clinical trials will not actually be
performed with Contract money but will rather be performed by the HVTN
with product delivered to them that was produced under the Contract.

**QUESTION 32.** I have a question regarding the budgeting of clinical
trials which we anticipate to be conducted by the HVTN. It is my
understanding that we should not include patient and central lab costs
in our budget. We also propose to use the AIDS Vaccine Evaluation Group
(AVEG).  Should we include the funding for immunological monitoring by
this NIH supported service.  We will include budget for Data Management,
Clinical Supply Management and related FTE costs to manage our
participation in the trial as well as travel to clinical sites.  Can you
clarify this issue of clinical trials run by the NIH supported
networks. 

**ANSWER** AVEG no longer exists.  It was replaced by the HVTN.  You
should not budget for trials to be conducted by the HVTN except: (1)
insofar as you incur costs delivering product and documentation (e.g.
that needed to support the IND application to the FDA) to the HVTN so
that the trial can be conducted, (2) for your own Data Management,
Clinical Supply Management and related FTE costs to manage participation
in the trial as well as travel to clinical sites (e.g. for your company
medical people), or (3) for your own analyses of samples if any are
desired in addition to the HVTN\'s analyses.