Anticoagulant Sodium Citrate 4% w/v Solution, U.S.P. - Summary Basis of Approval

Product:	Anticoagulant Sodium Citrate 4% w/v Solution, U.S.P. in Plastic Bag
Company:	Haemonetics Corporation 400 Wood Road Braintree, MA    02184
Date of Application:	January 22, 1998

 

2. Indications for Use
   The product is for use only with automated apheresis devices in the collection of human plasma or in performing therapeutic plasma exchange procedures. The 4% Sodium Citrate is metered by the apheresis machine into the collected whole blood, the plasma is collected into a plasma collection bag and the cellular components are returned to the donor. The anticoagulant is not to be infused directly into the donor.

    

    

3. Dosage Form:
   The 4% Sodium Citrate is used in an anticoagulant to whole blood ratio of 1:16. A flexible PVC plastic bag contains 250 mL of 4% Sodium Citrate and has a filling leg and a twist-off closure which accepts a spike from an apheresis collection set. The plastic bag is contained in an overwrap which is added prior to sterilization.

    

    

4. Manufacturing and Controls:

    

   1. Manufacturing:
      No new drug substance is involved in this NDA. The formulation for the 4% Sodium Citrate is in accordance with USP XXIII. The plastic bags are made by [------------]. The anticoagulant solution is manufactured and filled into bags at the Haemonetics Corporation facility in Union, SC. Testing is performed on the environment, raw materials, in-process and finished products to assure that appropriate requirements and specifications are met.

       

   2. Stability
      Data was submitted on three lots of product held at room temperature at 40^°C for 6 months. [---------------------- ----------------- ---------------- --------- ------------------- -------------------- ---------------- ---------------].

       

       

   3. Methods Validation
      All critical manufacturing steps, including sterilization and all systems have been successfully validated and are part of the NDA.

       

       

   4. Labeling:
      Draft labeling has been submitted. No trade name is being used. The Directions for Use are contained in the appropriate apheresis machine manual.

       

       

   5. Establishment Inspection:
      The Union, SC facility had a Pre-Approval Inspection for Dextrose 5% Injection, USP May 2-6, and June 29, 1994. The facility had a regularly scheduled inspection March 17-20, 1997.

       

       

   6. Environmental Impact Statement:
      4% Sodium Citrate solution is exempted per 21 CFR 25.24(c)(4).

       

    

5. Pharmacokinetics / Bioavailability:
   Since no new drug substance is involved in the 4% Sodium Citrate and the bag has been used extensively in Europe with this and other anticoagulants, no pharmacokinetic or bioavailability data are included.

    

    

6. Clinical Data:
   During a meeting between Haemonetics and members of the CBER staff it was agreed that no clinical studies would be necessary.

    

    

7. Safety and Efficacy:
   Haemonetics has sold over [---------] units of 4% Sodium Citrate with its name on the product since April, 1997. During that time no serious adverse reports have been received and no recalls of this 4% Sodium Citrate have been necessary. Reprints are included in the NDA to offer further proof of the safety and efficacy of 4% Sodium Citrate.

    

   -- signature --	2/28/2000
   Betsy Poindexter	Date
   -- signature --	2/29/2000
   Edward Tabor, M.D.	Date