April 14, 2009
Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852
RE Docket 2008-D-0659, 16 January 2009, “Guidance for Industry: Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)”
Dear FDA Dockets Manager:
AABB is an international association dedicated to advancing transfusion and cellular therapies worldwide. Our members include more than 1,800 hospital and community blood centers and transfusion and transplantation services as well as approximately 8,000 individuals involved in activities related to transfusion, cellular therapies and transplantation medicine. For over 50 years, AABB has established voluntary standards for, and accredited institutions involved in, these activities. AABB is focused on improving health through the advancement of science and the practice of transfusion medicine and related biological therapies, developing and delivering programs and services to optimize patient and donor care and safety.
AABB chartered a group of cellular therapy experts to review the draft guidance document, “Guidance for Industry: Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)”. Overall, the group commends FDA on the format and content of the draft guidance. The real-life examples provided in the document will benefit our members when determining how to implement the regulations. Section III. CGTP Requirements, E. will be very valuable when determining if the product is regulated solely under current GTPs or must also follow current GMPs. However, there are several areas that we feel would benefit from some wording modification or additional clarification.
The comments are arranged in the following format:
Section – language from draft guidance reprinted with page # and other identifying information.
Recommendation/Request for Clarification – recommendation or clarification request.
Background – rationale with information supporting the recommendation/clarification request.
SECTION III. CGTP REQUIREMENTS (§ 1271.150), C. How do I ensure that another establishment with which I have a contract, agreement or other arrangement complies with CGTP requirements? (pages 4-5): "Under § 1271.150(c)(I)(iii), before entering into a contract, agreement, or other arrangement with another establishment to perform any step in manufacture for you, you must ensure that the establishment complies with applicable CGTP requirements.”
Request for Clarification - We agree that an establishment that enters into an agreement with another establishment to perform any step in manufacturing should ensure the contracted establishment complies with applicable cGTP requirements. However, the roles of a coordinating registry may not meet the traditional definition of a contracted manufacturing establishment. For clarity, we request that an additional example be included to illustrate the extent of oversight required when enlisting the services of a coordinating registry.
SECTION VI. PERSONNEL (§ 1271.170), B. How would I ensure that personnel have the necessary education, experience and training to perform their job?, Bullet number two (page 16): “setting up a program for demonstration of competency for their assigned functions when observed by a supervisor.”
Recommendation – Reword the sentence to read, “setting up a program for demonstration of competency for their assigned functions when observed by a supervisor or designee.”
Background – The observation of tasks for competency assessment is not generally limited to supervisory personnel. There are many establishments that utilize training departments or a designated qualified person to accomplish competency assessments.
SECTION XI. SUPPLIES AND REAGENTS (§ 1271.210), B. What verification is required for supplies and reagents?, Paragraph two (page 27): “We recommend that you keep product information data sheets for all supplies and reagents used, update these sheets as products change, and keep an archive of previously used products. Verification that reagents meet specifications may be accomplished either by reviewing the Certificate of Analysis (COA) or by performing relevant testing. For supplies such as sterile drapes or gloves that are not expected to have a COA, we recommend that you obtain information from the vendor on the relevant specifications and the manufacturing process for the supply, including any sterilization process.”
Recommendation – Reword the last sentence to read, “For supplies such as sterile drapes or gloves that are not expected to have a COA, we recommend that you obtain information from the vendor on the relevant specifications”.
Background – As currently written, “For supplies such as sterile drapes or gloves that are not expected to have a COA, we recommend that you obtain information from the vendor on the relevant specifications and the manufacturing process for the supply, including any sterilization process.”, allows for a vast interpretation as to the extent of supplier information that should be obtained. To require an establishment to maintain information on the manufacturing process for the supplier would be cumbersome and provide no increase in the quality/safety of the supplies. We believe that maintaining a copy of the relevant product specifications in conjunction with a supplier qualification process would provide adequate assurance of the safety and potency of supplies and reagents.
SECTION XIII. PROCESSING AND PROCESS CONTROLS (§ 1271.220), A. What is processing?, (page 32): “Under § 1271 .3(ff), processing means any activity performed on an HCT/P, other than recovery, donor screening, donor testing, storage, labeling, packaging, or distribution, such as:
· testing for microorganisms;
· steps to inactivate or remove adventitious agents;
· preservation for storage; and
· removal from storage.”
Request for Clarification – The term ‘preparation’ is vague and can be interpreted in many ways. To avoid confusion and promote consistency of understanding, clarify the meaning of the word in this context with either a definition or specific examples. Many establishments still struggle with the interpretation and implementation of current Good Tissue Practices. These establishments would benefit greatly from clarity and examples of ‘preparation’ and when such ‘preparation’ is considered manufacturing.
SECTION XIII. PROCESSING AND PROCESS CONTROLS (§ 1271.220), D. Why are pre-processing (microbiological) cultures important?, (page 34): “We believe that preprocessing cultures should be conducted because they are a critical in-process control for musculoskeletal (e.g., bone, tendon, ligament) HCT/Ps.”
Recommendation – Reword the last sentence to read, “We believe that preprocessing cultures for musculoskeletal (e.g., bone, tendon, ligament) HCT/Ps should be conducted because they are a critical in-process control.”
Background – It is evident from the remaining paragraph, that the recommendation for preprocessing cultures is for musculoskeletal HCT/Ps; however the sentence mentioned above is somewhat ambiguous. The proposed rewording clarifies the sentence and ensures consistency with the remainder of the paragraph.
SECTION XVIII. RECEIPT, PRE-DISTRIBUTION SHIPMENT, AND DISTRIBUTION OF AN HCT/P (§ 1271.265), L. Is an establishment such as a hospital that only receives and stores HCTP/s required to register under § 1271.1(b)?, (page 46): “In accordance with § 1271.l5(d), a hospital that only receives or stores HCT/Ps solely for implantation, transplantation, infusion, or transfer within its facility, but does not recover, screen, test, process, label, package, or distribute HCT/Ps, is not required to register.
However, if a hospital sends the HCT/P to other establishments (e.g., other hospitals or ambulatory sites), the hospital is functioning as a distributor and is required under § l27l.l(b) to register and list its HCT/Ps.”
Request for Clarification – Request that the second paragraph be expanded to include example(s) of what processing would require an establishment to register and list its HCT/Ps. Processing as defined depends on what manipulation is performed and where the activity occurs. This concept is an area that is not completely understood by establishments and they would benefit greatly from an expanded section on this topic.
Joseph L. Giglio, MS, MT(ASCP)SBB, CSQE(ASQ)CQA
Deputy Director, Regulatory Affairs