Joint Statement on National Drug Code for HCT/Ps – 12/11/06 

Requirements for Foreign and Domestic Establishment Registration and Listing for Human Drugs, Including Drugs That Are Regulated Under a Biologics License Application, and Animal Drugs: Proposed Rule

Public Meeting

December 11, 2006

 M. Allene Carr-Greer, MT, ASCP(SBB)

Deputy Director, Regulatory Affairs, AABB

National Drug Codes for HCT/Ps

AABB, America’s Blood Centers (ABC), American Red Cross (ARC), American Society for Blood and Marrow Transplantation (ASBMT), Foundation for the Accreditation of Cellular Therapy (FACT), ICCBBA, International Society for Cellular Therapies (ISCT), and National Marrow Donor Program (NMDP) wishes to thank the Food and Drug Administration (FDA) for the opportunity to speak at today’s meeting. We support FDA’s ongoing efforts to improve the safety of human drugs and biologic products.  Today we will address the proposed requirement to implement the National Drug Code (NDC) system for licensed Human Cells, Tissues and Cellular and Tissue-Based Products (HCT/Ps), and in particular hematopoietic progenitor cells (HPCs) collected from peripheral or cord blood and therapeutic cells (TC) as described in Attachment A.  A requirement to implement the NDC system for these products will create a duplicate tracking system that will not provide increased patient safety but in fact may detract from the current level of patient safety. 

Today, and in comments to the docket for Requirements for Foreign and Domestic Establishment Registration and Listing for Human Drugs, Including Drugs that are Regulated Under a Biologics License Application, and Animal Drugs (Docket No. 2005N-0403, August 29, 2006), we will provide justification for requesting that these products be exempt from any requirement to use the NDC system as outlined in 21 CFR Part 201, Subpart 201 and Part 207, Subpart C and D.  The exemption is requested under proposed 21 CFR Part 201, Subpart A, Section 201.25(d)(1)(ii). It is our position that the NDC system is not a good fit for the products identified in this request, and that manufacturers of the products and the consignees receiving them for patient infusion and or transplantation are already implementing a system that was developed specifically for them.  In support of our request for an exemption we offer the following comments today.

NDC - Square Peg For A Round Hole

·         Due to the biological nature of the products and manufacturing process, a manufacturer must have the ability to attain NDC identifiers within minutes of collection, 24 hours a day, 7 days a week.  Most of these products are infused within hours of collection.  Recipients are being prepped and irradiated while the products are being collected and transported.  Products are generally en-route to the consignee before all the data that would be required to obtain an NDC number from FDA is even available.  Currently, the data is often faxed to arrive at the site of infusion / transplantation by the time the product arrives.  The integrity of the product may be compromised if delayed due to a delay in obtaining an NDC number.  This could result in a less safe and efficacious product being available for the patient.

·         The products have variable contents (quantities of active and inactive ingredients) as opposed to a drug that would have a specified concentration of the active and inactive ingredients; thus, each HPC or TC would be a lot unto itself and require that the manufacture obtain a different NDC number.  As stated above the contents of each of these unique products that must be available in order to obtain the NDC number is most often not available before the product must be transported to the consignee.

·         HPCs and TCs are unique products.  They are not mass-produced in lots like other drugs. Indeed it is much more likely that each product is collected for and, tailored to, a particular patient’s needs. Transcription and dispensing errors are very unlikely to occur due to the small volume of product that is given and the limited number of patients that would be receiving the treatment.

·         HPCs and TCs are not similar to other drugs covered by the NDC requirements of this proposed rule or the rule on bar codes. They do not fit the NDC system, or the other databases described throughout the proposed rule.

·         The process of having to obtain an NDC for each product and potentially, each processing step, would impose an undue burden on the manufacturer with no positive impact on patient safety.

·         DailyMed searches could not be performed by a patient or patient advocate using the NDC number because the patient and/or physician would not have the NDC number until immediately prior to the infusion.  There would be no existing database of information for the product that could be searched and thus no improvement to patient safety by better access to medication information through the DailyMed initiative.

·         In general, cellular therapy products will have been infused before the NDC number is populated in any federally maintained database.  Adverse reactions that occur with the patient after infusion are already required to be reported to FDA via MedWatch Form FDA 3500A.  This form recognizes the use of a “unique #” for product identification, and does not require use of the NDC number.

ISBT 128 Standard
 

·         The ISBT 128 international information standard provides a globally unique product identifier.  This standard provides greater benefits and patient safety than an NDC. 

·         Currently, all major standard-setting organizations for Cellular Therapy have committed themselves to the use of the ISBT 128 as an industry standard.  An international Cellular Therapy Coding and Labeling Advisory Group has convened due to recognition by the parties involved that widespread use of the ISBT 128 standard in the fields of blood transfusion and transplantation has already occurred.  Organizations represented in the advisory group include AABB, ASBMT, EBMT, FACT, ICCBBA, ISBT/SITS, ISCT, ISCT Europe, JACIE, NMDP and WMDA.

·         ISBT 128 is an internationally recognized information standard – use of this labeling system would ensure that all imported and exported products using this system could be read by the current computer systems.

·         Facilities that manufacture and infuse HPCs and TCs are very familiar with the ISBT 128 standard because this is the labeling system being used in hospital laboratories and transfusion services as well as cellular therapy processing laboratories.

·         The original manufacturer’s information and traceability to the donor will never be lost due to re-labeling.  The NDC system requires the product to have a new facility/product code assigned as it moves through the collection, processing and distribution systems.  The ISBT labeling system, that does not require recoding the manufacturer ID, will decrease the transcription error rate and increase trackability of the product. In addition, in the ISBT system the product code, which must be changed as the product is further processed, is not tied to the manufacturer ID and can thus be changed without disturbing the trackability of the product.

·         ISBT 128 labeling system contains more information than NDC, therefore can afford a better tracking and tracing mechanism of the product thus facilitating a quicker recall, improvements in deviation management, reporting of adverse events and outcome follow-up.

·         ISBT-128 labeling provides

o        Unique facility identifiers (original manufacturer never needs to be re-coded)

o        Lot number relating to the donor (globally unique)

o        Product code (including multiple / different products from same donation)

o        ABO and Rh of the donor

o        Expiration date

o        Additional attributes of the cellular product

Negative impact of implementing NDC system

·         Current cellular therapy processing and hospital laboratory computer systems are not designed to accommodate the reading and incorporation of NDC information.  New computer systems will be needed by manufacturers and hospitals.  Minimally, current systems will require major upgrades.  It is hard to say at this point what the gaps are as the system explained in the proposed rule is not operational.  While pharmacy computer systems may accommodate NDCs, cellular therapy processing and hospital laboratory systems are unlikely to do so.

·         Due to the small package size of some products, the NDC label would have to be attached to the product, not adhered to the product.

·         Loss of standardization will occur due to similar products (varying only by minor differences in cell counts or inactive ingredients) having different product codes even when manufactured by the same organization. 

·         There may be a need to include an identifier to show multiple products from the same donation. NDC cannot accommodate the various attributes of cellular products.  Once again, ISBT 128 has given consideration to the very unique nature of cellular therapy products and is addressing these through the Cellular Therapy Coding and Labeling Advisory Group.

·         A requirement to implement NDCs is a de facto requirement to maintain duplicate systems for HPCs and TCs.  ISBT 128 labels are essential to the success of importing and exporting cellular therapy products.  NDCs are specific to the U.S. and would be meaningless on an exported product.  NDCs do not contain the information necessary to document and track the collection, processing, distribution and infusion of these products.

·         Maintaining these duplicative systems is overly burdensome and adds nothing to patient safety.  It will result in resources being directed away from processes and initiatives that can add to patient safety.

·         NDC makes no provision for the encoding of a donor registry.  NMDP currently adheres to the confidentiality provisions of the C.W. Bill Young Cell Transplantation Program to protect the identity of donor centers / apheresis collection sites.  [42 U.S.C. § 274k(f)(5)]

FDA is proposing use of a system that has yet to be developed by the agency.  However, the cellular therapy community has been proactive over the last years in assessing the need for labeling HPC and TC products in a manner to support accurate and complete tracking of the product from the time of collection, through various manufacturing processes, during storage and transport to the consignee and ultimately to patient infusion.

The ISBT 128 standard was voluntarily selected for use by the cellular therapy community prior to any proposals made by FDA.  The community has invested much time and money in developing the system as well as implementation plans.  A careful review of the facts indicate that use of the NDC numbering system in addition to the already existing ISBT-128 system does not offer any increase in patient safety.  In fact we would argue that implementing NDC codes for HPCs and TCs will hinder the progress of implementing the superior ISBT 128 information standard for these products. To require these products to also be labeled with NDCs would force manufacturers to redirect very limited resources in order to implement a new manufacturing process that offers no benefit to patient safety and would be overly burdensome.  NDC will not replace the need to use ISBT 128 and the requirement to track using two different labeling systems will ultimately have a negative impact on patient safety and will open the manufacturing processes to many opportunities for error.

The organizations represented by this statement strongly support initiatives that improve the safety of patients and donors and stand ready to interact with the FDA as necessary.   Today we ask that FDA carefully consider patient safety issues when evaluating the position put forth in this statement. We believe that the National Drug Code system is not a viable option for improving the safety of hematopoietic progenitor cells and therapeutic cells and that they should be exempt from requirements found in 21 CFR Part 201 and 207 for the use of the NDC system.

Attachment A