Document:

AMENDMENT NO. 2

         THIS AMENDMENT NO. 2 (this "Amendment") dated as of March 1, 2000, to
the Loan Agreement referenced below, is by and among PHARMACEUTICAL PRODUCT
DEVELOPMENT, INC., a North Carolina corporation, the subsidiaries and affiliates
identified on the signature pages hereto and FIRST UNION NATIONAL BANK. Terms
used but not otherwise defined shall have the meanings provided in the Loan
Agreement.

                               W I T N E S S E T H

         WHEREAS, a $50 million credit facility has been established in favor of
Pharmaceutical Product Development, Inc., a North Carolina corporation (the
"Borrower"), pursuant to the terms of that Loan Agreement dated as of June 24,
1998 (as amended and modified, the "Loan Agreement") among the Borrower, the
Guarantors identified therein and First Union National Bank (the "Bank");

         WHEREAS, the Borrower has requested certain modifications to Loan
Agreement;

         WHEREAS, the Bank has agreed to the modifications on the terms and
conditions set forth herein;

         NOW, THEREFORE, IN CONSIDERATION of the premises and other good and
valuable consideration, the receipt and sufficiency of which is hereby
acknowledged, the parties agree as follows:

         1. In Section 6.9 of the Loan Agreement, subsections (f) and (g) are
renumbered as (h) and (i), respectively, thereof and new subsections (f) and (g)
are added thereto to read as follows:

                  (f) cash equity investments in and to ADoctorInYourHouse.com,
                  Inc. in an aggregate principal amount (on a cost basis) not to
                  exceed $5,000,000 at any time;

                  (g) loans and advances to NeoRx Corporation in an aggregate
                  principal amount not to exceed $5,000,000 at any time;

         2. The reference to "June 25, 1997" on the third line of the second
paragraph on page 1 of Amendment No. 1 to the Loan Agreement, which Amendment
No. 1 is dated January 30, 1999, is changed to "June 24, 1998".

         3. This Amendment shall be effective upon execution of this Amendment
by the Credit Parties and the Bank.

         4. Except as modified hereby, all of the terms and provisions of the
Loan Agreement (including Schedules and Exhibits) shall remain in full force and
effect.

         5. The Borrower agree to pay all reasonable costs and expenses of the
Bank in connection with the preparation, execution and delivery of this
Amendment, including without limitation the reasonable fees and expenses of
Moore & Van Allen, PLLC.
<PAGE>

         6. This Amendment may be executed in any number of counterparts, each
of which when so executed and delivered shall be deemed an original and it shall
not be necessary in making proof of this Amendment to produce or account for
more than one such counterpart.

         7. This Amendment shall be deemed to be a contract made under, and for
all purposes shall be construed in accordance with the laws of the State of
North Carolina.

         IN WITNESS WHEREOF, each of the parties hereto has caused a counterpart
of this Amendment to be duly executed and delivered as of the date first above
written.

BORROWER:                           PHARMACEUTICAL PRODUCT DEVELOPMENT, INC.,
                                    a North Carolina corporation

                                    By:    /s/ Fredric N. Eshelman
                                        ------------------------------
                                    Name: Fredric N. Eshelman
                                    Title: Chief Executive Officer

GUARANTORS:                         PPD DEVELOPMENT, INC.,
                                    a Texas corporation

                                    By:   /s/ Fredric N. Eshelman
                                        ------------------------------
                                    Name: Fredric N. Eshelman
                                    Title: Chief Executive Officer

BANK:                               FIRST UNION NATIONAL BANK

                                    By:  /s/ G. Mendel Lay, Jr.
                                        ------------------------------
                                    Name:  G. Mendel Lay, Jr.
                                    Title:   Sr. V.P.FOURTH AMENDMENT TO LOAN AGREEMENT

                  THIS FOURTH AMENDMENT TO LOAN AGREEMENT (this "Amendment") is
made as of the 23rd day of February, 2000, by and among PHARMACEUTICAL PRODUCT
DEVELOPMENT, INC., a North Carolina corporation (together with its successors,
the "Borrower"); PPD DEVELOPMENT, INC., (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, and a Third Amendment to Loan
Agreement dated as of November 11, 1999 (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. AMENDMENT. Effective from and after February 23,
2000, the Loan Agreement is hereby amended as follows:

                           2.1 In Section 6.9 subsections (g) and (h) are
re-lettered as (h) and (i), respectively, and a new subsection (g) is hereby
added to Section 6.9 of the Loan Agreement to read as follows:

                  "(g) Investments in and to NeoRx in an aggregate principal
amount (on a cost basis) not to exceed $5,000,000 at any time;"
<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 Guarantor authorized to
         execute and deliver this Amendment;

                  (c) 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, 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.

                  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.

                                      -2-
<PAGE>

                  (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 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>

                  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                   By:   /s/ Fred N. Eshelman
--------------------------                      ----------------------------
       Secretary                            Title:   Chief Executive Officer
--------------------------                         -------------------------

[CORPORATE SEAL]

                                            BANK:

                                            WACHOVIA BANK, N.A.

                                            By:   /s/ Keith Sherman
                                                ----------------------------
                                            Title:   Sr. Vice President
                                                   -------------------------

                                            GUARANTOR:

ATTEST:                                     PPD DEVELOPMENT, INC.

/s/ Fred B. Davenport, Jr.                  By:   /s/  Fred N. Eshelman
--------------------------                      ----------------------------
       Secretary                            Title:   Chief Executive Officer
--------------------------                         -------------------------

[CORPORATE SEAL]

                                      -4-

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