Document:

EXHIBIT 10.153
                        FIFTH AMENDMENT TO LOAN AGREEMENT

                  THIS FIFTH AMENDMENT TO LOAN AGREEMENT (this "Amendment") is
made as of the 1st day of August, 2000, by and among PHARMACEUTICAL PRODUCT
DEVELOPMENT, INC., a North Carolina corporation (together with its successors,
the "Borrower"); PPD DEVELOPMENT, LLC, a Texas limited liability company,
formerly PPD DEVELOPMENT, INC., a Texas corporation formerly known as PPD
PHARMACO, INC., a Texas corporation (the "Guarantor"); and WACHOVIA BANK, N.A.,
a national banking association (together with its endorsees, successors and
assigns, the "Bank").

                                R E C I T A L S:

                  The Borrower, the Guarantor and the Bank are parties to a
certain Loan Agreement dated as of August 7, 1997, as amended pursuant to an
Amendment to Loan Agreement dated as of August 6, 1998, a Second Amendment to
Loan Agreement dated as of January 30, 1999, a Third Amendment to Loan Agreement
dated as of November 11, 1999, and a Fourth Amendment to Loan Agreement dated as
of February 23, 2000 (the "Loan Agreement").

                  Capitalized terms used in this Amendment which are not
otherwise defined in this Amendment shall have the respective meanings assigned
to them in the Loan Agreement.

                  The Borrower has requested certain modifications to the Loan
Agreement and the Bank is willing to modify the Loan Agreement subject to the
terms, provisions and conditions set forth in this Amendment.

                  NOW, THEREFORE, in consideration of the Recitals, the mutual
promises herein contained and other good and valuable consideration, the receipt
and sufficiency of which are hereby acknowledged, the Borrower, the Guarantor
and the Bank, intending to be legally bound hereby, agree as follows:

                  SECTION 1. Recitals. The Recitals are incorporated herein by
reference and shall be deemed to be a part of this Amendment.

                  SECTION 2. Amendments. Effective from and after August 3,
2000, the Loan Agreement is hereby amended as follows:

                  2.1 Extension of Termination Date. The Termination Date is
hereby extended from August 3, 2000 to August 2, 2001.

                  2.2 Replacement of Schedule I. Schedule I to the Loan
Agreement lists PPD Pharmaco, Inc. and APBI Environmental Sciences Group, Inc.
as Material Subsidiaries. APBI Environmental Sciences Group, Inc. is no longer a
subsidiary of the Borrower and Schedule I attached to the Loan Agreement is
hereby replaced with Schedule I attached to this Amendment and made a part of
this Amendment and the Loan Agreement by this reference.

<PAGE>

                  SECTION 3. Conditions to Effectiveness. The effectiveness of
this Amendment and the obligations of the Bank hereunder are subject to receipt
by the Bank of the following:

                  (a) an original Amendment, duly executed by the Borrower and
         the Guarantor;

                  (b) a certificate of incumbency satisfactory to the Bank,
         certifying as to the names, true signatures and incumbency of the
         officer or officers of the Borrower and the members or managers of the
         Guarantor authorized to execute and deliver this Amendment;

                  (c) a certificate of existence issued by the Texas Secretary
         of State for PPD Development, LLC, together with a true and complete
         copy of its operating agreement and filed Articles of Organization, and
         copies of the documents evidencing and approving the conversion;

                  (d) such other documents or items as the Bank or its counsel
         may reasonably request.

The effectiveness of this Amendment and the obligations of the Bank hereunder
are further subject to the condition that no Event of Default or event or
condition which with notice or lapse of time, or both, would constitute an Event
of Default under the Loan Agreement, as hereby amended, shall have occurred and
be continuing, and the representations and warranties contained in Section 5 of
the Loan Agreement, as amended herein, are true on and as of the date hereof.

                  SECTION 4. No Other Amendment. Except for the amendments set
forth above, the Loan Agreement shall remain unchanged and in full force and
effect. This Amendment is not intended to effect, nor shall it be construed as,
a novation. The Loan Agreement and this Amendment shall be construed together as
a single agreement. Nothing herein contained shall waive, annul, alter, limit,
diminish, vary or affect any provision, condition, covenant or agreement
contained in the Loan Agreement, except as herein amended, nor affect or impair
any rights, powers or remedies under the Loan Agreement as hereby amended. The
Bank does hereby reserve all of its rights and remedies against all parties who
may be or may hereafter become secondarily liable for the repayment of the Loan.
The Borrower and the Guarantor promise and agree to perform all of the
requirements, conditions, agreements and obligations under the terms of the Loan
Agreement, as hereby amended, the Loan Agreement, as amended, and the Guaranty
contained in the Loan Agreement, being hereby ratified and affirmed. The
Borrower and Guarantor hereby expressly agree that the Loan Agreement, as
amended, is in full force and effect and confirm that they have no set off,
counterclaim or defense with respect to the Loan Agreement, the Loan, the Note,
the Guaranty contained in the Loan Agreement or the Guaranteed Obligations.

                                      -2-
<PAGE>

                  SECTION 5. Representations and Warranties. The Borrower and
the Guarantor hereby represent and warrant to the Bank as follows:

                  (a) No Event of Default or event or condition which with
         notice or lapse or time, or both, would constitute an Event of Default
         under the Loan Agreement, as hereby amended, has occurred and is
         continuing on the date hereof.

                  (b) The representations and warranties contained in Section 5
         of the Loan Agreement, as amended herein, are true on and as of the
         date of this Amendment.

                  (c) This Amendment has been duly authorized, validly executed
         and delivered by one or more authorized officers of the Borrower and
         the Guarantor, and constitutes the legal, valid and binding obligation
         of the Borrower and Guarantor enforceable against them in accordance
         with its terms.

                  (d) The execution and delivery of this Amendment and the
         Borrower's and the Guarantor's performance hereunder do not and will
         not require the consent or approval of any regulatory authority or
         governmental authority or agency having jurisdiction over the Borrower
         or the Guarantor, nor be in contravention of or in conflict with the
         Articles of Incorporation or Bylaws of the Borrower or the operating
         agreement or Articles of Organization of the Guarantor, or the
         provision of any statute, or any judgment, order or indenture,
         instrument, agreement or undertaking to which the Borrower or the
         Guarantor is party or by which the Borrower's or the Guarantor's assets
         or properties are or may become bound.

                  SECTION 6. Counterparts. This Amendment may be executed in
counterparts, each of which shall be deemed to be an original and all of which,
taken together, shall constitute one and the same agreement.

                  SECTION 7. Governing Law. This Amendment shall be deemed to be
made pursuant to the laws of the State of North Carolina with respect to
agreements made and to be performed wholly in the State of North Carolina and
shall be construed, interpreted, performed and enforced in accordance therewith.

                  SECTION 8. Costs and Expenses. The Borrower shall pay any and
all out-of-pocket expenses in connection with the preparation, execution and
delivery of this Amendment, including, without limitation, the fees and expenses
of the Bank's counsel in connection therewith.

                  SECTION 9. Entire Agreement. This Amendment contains the
entire agreement of the parties with respect to the subject matter hereof, and
there are no representations, inducements or other provisions among the parties
regarding such subject matter other than those expressed herein in writing. All
changes, additions or deletions to this Amendment must be in writing and signed
by all parties.

                                      -3-
<PAGE>

                  SECTION 10. Guarantor Reaffirmation. PPD Development, Inc., a
Texas corporation, was converted to a Texas limited liability company effective
June 30, 2000 and is now known as PPD Development, LLC, a Texas limited
liability company and copies of all conversion documents have been provided to
the Bank. PPD Development, LLC hereby ratifies, reaffirms and confirms the
Guaranty contained in the Loan Agreement, as amended, and all of the Guaranteed
Obligations.

                  IN WITNESS WHEREOF, the parties hereto have caused their
respective duly authorized officers or representatives to execute and deliver
this Amendment as of the day and year first above written.

                                              BORROWER:

ATTEST:                                       PHARMACEUTICAL PRODUCT
                                              DEVELOPMENT, INC.

/s/  Fred B. Davenport, Jr.   Secretary       By:  /s/  Fredric N. Eshelman
-----------------------------                    ---------------------------
                                              Title:  Chief Executive Officer
                                                    --------------------------
[CORPORATE SEAL]

                                              BANK:

                                              WACHOVIA BANK, N.A.

                                              By:  /s/  Keith Sherman
                                                  -------------------
                                              Title: SVP
                                                    ----

                                              GUARANTOR:

                                              PPD DEVELOPMENT, LLC      (SEAL)

                                              By: /s/ Fredric N. Eshelman (SEAL)
                                                     ---------------------------
                                                                Manager

                                      -4-
<PAGE>

                                   Schedule I

                          List of Material Subsidiaries

PPD DEVELOPMENT, LLC, a Texas limited liability company, formerly PPD
DEVELOPMENT, INC., a Texas corporation formerly known as PPD PHARMACO, INC.(1)

--------
(1)      PPD PHARMACO, INC., a Texas corporation changed its name to PPD
         DEVELOPMENT, INC. and PPD DEVELOPMENT, INC., a Texas corporation
         converted to PPD DEVELOPMENT, LLC, a Texas limited liability company
         effective June 30, 2000.EXHIBIT 10.154

                                 LOAN AGREEMENT

         THIS LOAN AGREEMENT (the "Agreement") is made as of September 22, 2000
by and between PPGx, Inc., a Delaware corporation (the "Company") and the
entities whose names appear on the Schedule of Lenders attached hereto as
Exhibit A (the "Lenders").

         1.       The Loans.
                  ---------

                  1.1 The Loans. Subject to the conditions specified in this
Agreement, each Lender agrees to lend to the Company up to the sum set forth
opposite such Lender's name on Exhibit A (each, a "Credit Line," and
collectively, the "Total Credit Line"). Each month for the next nine months
prior to the Maturity Date (as defined below), the Company may borrow from the
Lenders the principal amount (each a "Loan Amount") up to one million dollars
($1,000,000); provided, however, that the Loan Amount shall be made on a pro
rata basis from the Lenders based on the Pro Rata Percentages set forth on
Exhibit A attached hereto. At the end of each month prior to the Maturity Date,
the Company will inform the Lenders in writing of the next month's Loan Amount
based on the Company's anticipated funding needs for the next month, and each
Lender will provide its Pro Rata Percentage, set forth on Exhibit A attached
hereto, of the Loan Amount on the second business day after receipt of the
notice of the Loan Amount. Each Loan Amount shall be made against the issuance
and delivery by the Company of a promissory note to each Lender for the portion
of the Loan Amount borrowed from each Lender (each a "Note," and collectively,
the "Notes") in substantially the form attached hereto as Exhibit B. The
availability of additional funding under these credit lines will be
automatically cancelled in the event of new external funding provided to the
Company or in case of a sale, merger or other disposition of the Company such
that after such event the Lenders collectively own less than fifty percent (50%)
of the outstanding securities of the Company.

                  1.2 Maturity Date. For the purposes of this Agreement, the
Maturity Date shall be the earlier of (i) June 30, 2001, or (ii) a sale, merger
or other disposition of the Company such that after such event the Lenders
collectively own less than fifty percent (50%) of the outstanding securities of
the Company.

                  1.3 Repayment. The Company will repay the outstanding
principal and accrued interest of each Note on a pro rata basis, so that each
Lender receives the same principal amount in repayment, and each Lender's share
of the outstanding aggregate Loan Amounts remains in accordance with the Pro
Rata Percentages set forth on Exhibit A attached hereto.

                  1.4 Place and Date of Closing. The closing of the transactions
provided for herein (the "Closing") will be held at the offices of
Pharmaceutical product Development, Inc. at 3151 South 17th Street, Wilmington,
NC 28412 on September 22, 2000 or at such other time and place as the parties
shall mutually agree (the "Closing Date").

                  1.5 Delivery. At the Closing, (i) the Company shall execute
and deliver to each Lender this Agreement, and (ii) the Lenders shall each
execute and deliver to the Company this Agreement.

                                       1
<PAGE>

         2.       Representations  and  Warranties of the Company.  The Company
hereby  represents and warrants to each Lender as follows:

                  2.1 Organization and Standing. The Company is a corporation
duly organized and validly existing under, and by virtue of, the laws of the
State of Delaware and is in good standing under such laws. The Company has the
requisite corporate power to own and operate its properties and assets, and to
carry on its business as presently conducted and as proposed to be conducted.

                  2.2 Corporate Power. The Company will have at the Closing all
requisite legal and corporate power to execute and deliver this Agreement, to
issue the Notes and to carry out and perform its obligations under the terms of
this Agreement.

                  2.3 Consents, Authorizations and Permits. The Company will
have obtained prior to the Closing any and all consents, authorizations and
permits appropriate or required in connection with the issuance of the Notes and
performance of the Company's obligations under the terms of this Agreement
(except for such consents, authorizations and permits that may be properly
obtained subsequent to the Closing).

                  2.4 Authorization. The execution, delivery and performance of
this Agreement by the Company has been duly authorized by all requisite
corporate action, and constitutes the valid and binding obligation of the
Company, enforceable against the Company in accordance with its terms, subject
to applicable bankruptcy, insolvency, reorganization, or similar laws relating
to or affecting the enforcement of creditors' rights.

         3.       Defaults and Remedies.
                  ---------------------

                  3.1 Events of Default. The following events shall be
considered Events of Default with respect to each Note:

                           (a) The Company shall default in the payment of any
part of the principal or accrued and unpaid interest on the Note for more than
thirty (30) days after the same shall become due and payable, whether at
maturity or at a date fixed for prepayment or otherwise;

                           (b) The Company shall make an assignment for the
benefit of creditors, or shall admit in writing its inability to pay its debts
as they become due, or shall file a voluntary petition for bankruptcy, or shall
file any petition or answer seeking for itself any reorganization, arrangement,
composition, readjustment, dissolution or similar relief under any present or
future statute, law or regulation, or shall file any answer admitting the
material allegations of a petition filed against the Company in any such
proceeding, or shall seek or consent to or acquiesce in the appointment of any
trustee, receiver or liquidator of the Company, or of all or any substantial
part of the properties of the Company, or the Company or its respective
directors or majority shareholders shall take any action looking to the
dissolution or liquidation of the Company; or

                                       2
<PAGE>

                           (c) Within sixty (60) days after the commencement of
any proceeding against the Company seeking any reorganization, arrangement,
composition, readjustment, liquidation, dissolution or similar relief under any
present or future statute, law or regulation, such proceeding shall not have
been dismissed or, within sixty (60) days after the appointment without the
consent or acquiescence of the Company of any trustee, receiver or liquidator of
the Company or of all or any substantial part of the properties of the Company,
such appointment shall not have been vacated.

                  3.2 Remedies. Upon the occurrence of an Event of Default under
Section 5.1 hereof, at the option and upon the declaration of the holder of the
Note, (i) the entire unpaid principal and accrued and unpaid interest on the
Note held by such holder shall, without presentment, demand, protest, or notice
of any kind, all of which are hereby expressly waived, be forthwith due and
payable, (ii) such holder may, immediately and without expiration of any period
of grace, enforce payment of all amounts due and owing under such Note and
exercise any and all other remedies granted to it at law, in equity, or
otherwise and (iii) the Applicable Rate (as defined in the form of Note attached
hereto as Exhibit B) will automatically change to the Default Rate of twelve
percent (12%) compounded quarterly in arrears.

         4.       Miscellaneous.
                  -------------

                  4.1 Waivers and Amendments. With the written consent of the
record holders of more than fifty percent (50%) of the aggregate Loan Amounts
then outstanding, the obligations of the Company and the rights of the holders
of the aggregate Loan Amounts under this Agreement may be waived (either
generally or in a particular instance, either retroactively or prospectively and
either for a specified period of time or indefinitely), and with the same
consent the Company, when authorized by resolution of its Board of Directors,
may enter into a supplementary agreement for the purpose of adding any
provisions to or changing in any manner or eliminating any of the provisions of
this Agreement; provided, however, that (i) no such waiver or supplemental
agreement shall reduce the above percentage of aggregate Loan Amounts, the
holders of which are required to consent to any waiver or supplemental
agreement, without the consent of the record or beneficial holders of all of the
aggregate Loan Amounts and (ii) no such waiver or supplemental agreement shall
vary the terms of the Notes (including without limitation the provisions of this
Agreement incorporated by reference into the Notes) without the consent of the
holder of the Note affected by such proposed waiver or supplemental agreement.
Upon the effectuation of each such waiver, consent, agreement, amendment or
modification the Company shall promptly give written notice thereof to the
record holders of the aggregate Loan Amounts who have not previously consented
thereto in writing. Neither this Agreement nor any provisions hereof may be
changed, waived, discharged or terminated orally, but only by a signed statement
in writing.

                  4.2 Governing Law. This Agreement shall be governed in all
respects by the laws of the State of Delaware as such laws are applied to
agreements between Delaware residents entered into and to be performed entirely
within Delaware.

                                       3
<PAGE>

                  4.3 Survival. The representations, warranties, covenants and
agreements made herein shall survive for a period of one year following the
Closing Date.

                  4.4 Successors and Assigns. Except as otherwise expressly
provided herein, the provisions hereof shall inure to the benefit of, and be
binding upon, the successors, assigns, heirs, executors and administrators of
the parties hereto.

                  4.5 Entire Agreement. This Agreement and the other documents
delivered pursuant hereto constitute the full and entire understanding and
agreement between the parties with regard to the subjects hereof and thereof.

                  4.6 Severability of this Agreement. In case any provision of
this Agreement shall be deemed to be invalid, illegal or unenforceable, the
validity, legality and enforceability of the remaining provisions shall not in
any way be affected or impaired thereby.

                  4.7 Titles and Subtitles. The titles of the Sections and
Subsections of this Agreement are for convenience of reference only and are not
to be considered in construing this Agreement.

                  4.8 Delays or Omissions. It is agreed that no delay or
omission to exercise any right, power or remedy accruing to the Lender, upon any
breach or default of the Company under this Agreement or the Notes, shall impair
any such right, power or remedy, nor shall it be construed to be a waiver of any
such breach or default, or any acquiescence therein, or of any similar breach or
default thereafter occurring; nor shall any waiver of any single breach or
default be deemed a waiver of any other breach or default theretofore or
thereafter occurring. It is further agreed that any waiver, permit, consent or
approval of any kind or character by the Lender of any breach or default under
this Agreement, or any waiver by the Lender of any provisions or conditions of
this Agreement must be in writing and shall be effective only to the extent
specifically set forth in writing and that all remedies, either under this
Agreement, or by law or otherwise afforded to the Lender, shall be cumulative
and not alternative.

                  4.9 Notices. Any notice or report required in this Agreement
or permitted to be given shall be given by depositing the same in the United
States mail, postage prepaid and addressed to the parties as follows:

                           To the Company:

                           PPGx, Inc.
                           3500 Paramount Parkway
                           Morrisville, NC 27560
                           Attn:  Josh Baker, President & CEO

                           To the Lenders:

                           At their respective addresses set forth on Exhibit A
                                                                      ---------

                                       4
<PAGE>

                  4.10 Counterparts. This Agreement may be executed by facsimile
and in any number of counterparts, each of which shall be deemed an original,
and all of which together shall constitute one instrument.

                  IN WITNESS WHEREOF, the parties have caused this Loan
Agreement to be duly executed and delivered as of the day and year first written
above.

                           [Signature Pages to Follow]

                                       5
<PAGE>

THE COMPANY:                            PPGx, INC.

                                        By:  /s/  Joshua S. Baker
                                             ----------------------
                                        Name:  Joshua S. Baker
                                             ----------------------
                                                (print)
                                        Title:  President / CEO
                                               -----------------------
                                        Address: 3500 Paramount Parkway
                                                 Morrisville, NC 27560

LENDERS:                                AXYS PHARMACEUTICALS, INC.

                                        By:  /s/  William J. Newell
                                             ----------------------
                                        Name:  William J. Newell
                                             ----------------------
                                                (print)
                                        Title:  Sr. Vice President
                                               -----------------------
                                        Address: 180 Kimball Way
                                                 S. San Francisco, CA 94080

                                        PHARMACEUTICAL PRODUCT DEVELOPMENT, INC.

                                        By:  /s/  Fred N. Eshelman
                                             ----------------------
                                        Name:  Fred N. Eshelman
                                             ----------------------
                                                (print)
                                        Title: Chief Executive Officer
                                               -----------------------
                                        Address: 3151 South 17th Street
                                                 Wilmington, NC 28412

                                       6
<PAGE>

<TABLE>
<CAPTION>
                                    EXHIBIT A

                                                   SCHEDULE OF LENDERS

------------------------------------------------ -------------------------------- ------------------------------
                       Lender                              Credit Line                 Pro Rata Percentage
------------------------------------------------ -------------------------------- ------------------------------
<S>                                                       <C>                                  <C>
Axys Pharmaceuticals, Inc.                                $3,150,000.00                        50%
180 Kimball Way
S. San Francisco, CA 94080
Attn: William J. Newell
------------------------------------------------ -------------------------------- ------------------------------
Pharmaceutical Product Development, Inc.                  $3,150,000.00                        50%
3151 South 17th Street
Wilmington, NC 28412
Attn: Fred Davenport, General Counsel
------------------------------------------------ -------------------------------- ------------------------------
TOTAL                                                     $6,300,000.00
------------------------------------------------ -------------------------------- ------------------------------
</TABLE>

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