610.53—Dating periods for licensed biological products.
(a) General.
The minimum dating periods in paragraph (c) of this section are based on data relating to usage, clinical experience, or laboratory tests that establish the reasonable period beyond which the product cannot be expected to yield its specific results and retain its safety, purity, and potency, provided the product is maintained at the recommended temperatures. The standards prescribed by the regulations in this subchapter are designed to ensure the continued safety, purity, and potency of the products and are based on the dating periods set forth in paragraph (c) of this section. Package labels for each product shall recommend storage at the stated temperatures.
(b) When the dating period begins.
The dating period for a product shall begin on the date of manufacture, as prescribed in § 610.50. The dating period for a combination of two or more products shall be no longer than the dating period of the component with the shortest dating period.
(c) Table of dating periods.
In using the table in this paragraph, a product in column A may be stored by the manufacturer at the prescribed temperature and length of time in either column B or C, plus the length of time in column D. The dating period in column D shall be applied from the day the product leaves the manufacturer's storage, provided the product has not exceeded its maximum storage period, as prescribed in column B or C. If a product is held in the manufacturer's storage beyond the period prescribed, the dating period for the product being distributed shall be reduced by a corresponding period.
| A | B | C | D |
|---|---|---|---|
| Product | Manufacturer's storage period 1 to 5 °C (unless otherwise stated) | Manufacturer's storage period 0 °C or colder (unless otherwise stated) | Dating period after leaving manufacturer's storage when stored at 2 to 8 °C (unless otherwise stated) |
| Adenovirus Vaccine Live Oral | 6 months | Not applicable | 6 months. |
| Albumin (Human) | 3 years | ......do | (a) 5 years. |
| ......do | ......do | (b) 3 years, provided labeling recommends storage at room temperature, no warmer than 37 °C. | |
| Not applicable | ......do | (c) 10 years, if in a hermetically sealed metal container and provided labeling recommends storage between 2 and 8 °C. | |
| Allergenic Extracts labeled “No U.S. Standard of Potency”: | |||
| 1. With 50 percent or more glycerin | 3 years | ......do | 3 years. |
| 2. With less than 50 percent glycerin | 18 months | ......do | 18 months. |
| 3. Products for which cold storage conditions are inappropriate | Not applicable | ......do | 18 months (from date of manufacture), provided labeling recommends storage at 30 °C or colder. |
| 4. Powders and tablets | ......do | ......do | 5 years (from date of manufacture), provided labeling recommends storage at 30 °C or colder. |
| 5. Freeze-dried products: | |||
| a. Unreconstituted | ......do | ......do | 4 years (from date of manufacture). |
| b. Reconstituted | ......do | ......do | 18 months (cannot exceed 4-year unreconstituted dating period plus an additional 12 months). |
| Allergenic Extracts, Alum Precipitated labeled “No U.S. Standard of Potency” | 18 months | ......do | 18 months. |
| Anthrax Vaccine Adsorbed | 2 years | ......do | 1 year. |
| Antibody to Hepatitis B Surface Antigen: | |||
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| 1. Antibody to Hepatitis B Surface Antigen | 6 months | ......do | 6 months. |
| 2. Lyophilized coated red blood cells | ......do | ......do | Do. |
| 3. Enzyme conjugated products | ......do | ......do | Do. |
| Iodinated (125l) products | Not applicable | ......do | 45 days (from date of manufacture). |
| Antihemophilic Factor (Human) | ......do | ......do | 1 year (from date of manufacture). |
| Anti-Human Globulin Liquid | ......do | ......do | 2 years. |
| Anti-Inhibitor Coagulant Complex | ......do | ......do | Do. |
| Antirabies Serum | 1 year | ......do | Do. |
| Antivenin (Crotalidae) Polyvalent | ......do | ......do | 5 years with an initial 10 percent excess of potency, provided labeling recommends storage at 37 ° C or colder. |
| Antivenin (Latrodectus Mactans) | ......do | ......do | 5 years with an initial 10 percent excess of potency. |
| Antivenin (Micurus fulvius) | ......do | ......do | Do. |
| Asparaginase | Not applicable | ......do | 18 months from the date of the last valid potency test. |
| BCG Vaccine | 1 year | Not applicable | 6 months. |
| Blood Grouping Reagents | |||
| 1. Liquid | Not applicable | Not applicable | 2 years. |
| 2. Dried | 1 year | 2 years | 5 years. |
| Blood Group Substance AB | ......do | ......do | 2 years. |
| Blood Group Substance A | ......do | ......do | Do. |
| Blood Group Substance B | ......do | ......do | Do. |
| Botulism Antitoxin | ......do | Not applicable | 5 years with an initial 20 percent excess of potency. |
| Cholera Vaccine | ......do | ......do | 18 months. |
| Coccidioidin | ......do | ......do | 3 years. |
| Collagenase | Not applicable | ......do | 4 years (from date of manufacture), provided labeling recommends storage at 37 °C or colder. |
| Cryoprecipitated AHF | ......do | ......do | 12 months from the date of collection of source blood, provided labeling recommends storage at −18 °C or colder. |
| Diphtheria Antitoxin: | |||
| 1. Liquid | 1 year | ......do | 5 years with an initial 20 percent excess of potency. |
| 2. Dried | ......do | 2 years | 5 years with an initial 10 percent excess of potency. |
| Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed | ......do | Not applicable | 18 months. |
| Diphtheria and Tetanus Toxoids, Adsorbed | ......do | ......do | 2 years. |
| Diphtheria Toxin for Schick Test | ......do | ......do | 1 year. |
| Diphtheria Toxoid | ......do | ......do | 2 years. |
| Diphtheria Toxoid Adsorbed | ......do | 2 years | Do. |
| Diphtheria Toxoid-Schick Test Control | Not applicable | Not applicable | 1 year. |
| Factor IX Complex | ......do | ......do | 1 year (from date of manufacture). |
| Fibrinolysin (Human) | 1 year | 2 years | 2 years. |
| Fibrinolysin and Desoxyribonuclease Combined (Bovine) | ......do | ......do | 3 years, provided labeling recommends storage at 30 °C or colder. |
| Fibrinolysin and Desoxyribonuclease Combined (Bovine) with Chloramphenicol | ......do | ......do | Do. |
| Hepatitis B Surface Antigen: | |||
| 1. Unlyophilized coated red blood cells | Not applicable | ......do | 14 days (from date of manufacture). |
| 2. Iodinated (125 l) product | ......do | ......do | 45 days (from date of manufacture). |
| 3. Enzyme conjugated product | 6 months | ......do | 6 months. |
| Histoplasmin | 1 year | Not applicable | 2 years. |
| Immunoglobulins: | |||
| 1. Hepatitis B Immune Globulin (Human) | Not applicable | ......do | 1 year. |
| 2. Immune Globulin (Human) | 3 years | ......do | 3 years. |
| 3. Immune Globulin Intravenous (Human) | Not applicable | ......do | 1 year. |
| 4. Lymphocyte Immune Globulin, Anti-Thymocyte Globulin (Equine) | ......do | Not applicable | 2 years. |
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| 5. Pertussis Immune Globulin (Human) | 3 years | ......do | 3 years from date the dried or frozen bulk product is placed in final solution. |
| 6. Rabies Immune Globulin (Human) | 1 year | ......do | 1 year. |
| 7. Rho(D) Immune Globulin (Human) | 6 months | ......do | 6 months. |
| 8. Tetanus Immune Globulin (Human) | 1 year | ......do | 3 years with an initial 10 percent excess of potency. |
| 9. Vaccinia Immune Globulin (Human) | 3 years | ......do | 3 years. |
| 10. Varicella-Zoster Immune Globulin (Human) | Not applicable | ......do | 1 year. |
| Hepatitis B Vaccine | 2 years at 2 to 8 °C | Not applicable | 3 years. |
| Influenza Virus Vaccine | 1 year | ......do | 18 months. |
| Limulus Amebocyte Lysate | Not applicable | Not applicable | 18 months (from date of manufacture). |
| Measles, Mumps, and Rubella Virus Vaccine Live | ......do | 1 year (−20 °C or colder) | 1 year. |
| Measles and Mumps Virus Vaccine Live | ......do | ......do | 1 year. |
| Measles and Rubella Virus Vaccine Live | ......do | ......do | Do. |
| Measles Live and Smallpox Vaccine | Not applicable | ......do | 1 year (from date of manufacture). |
| Measles Virus Vaccine Live | ......do | ......do | 1 year. |
| Meningococcal Polysaccharide Vaccine Group A: | |||
| 1. Final bulk powder | ......do | 2 years (−20 °C or colder) | Not applicable. |
| 2. Final container | Not applicable | 3 years (−20 °C or colder) | 2 years. |
| Meningococcal Polysaccharide Vaccine Group C: | |||
| 1. Final bulk powder | ......do | 2 years (−20 °C or colder) | Not applicable. |
| 2. Final container | ......do | 3 years (−20 °C or colder) | 2 years. |
| Meningococcal Polysaccharide Vaccine Groups A and C combined: | |||
| 1. Final bulk powder | ......do | 2 years (−20 °C or colder) | Not applicable. |
| 2. Final container | ......do | 3 years (−20 °C or colder) | 2 years. |
| Meningococcal Polysaccharide Vaccine Groups A, C, Y, and W135 combined: | |||
| 1. Final bulk power | ......do | 2 years (−20 °C or colder) | Not applicable. |
| 2. Final container | ......do | 3 years (−20 °C or colder) | 2 years. |
| Mumps Skin Test Antigen | 6 months | Not applicable | 18 months. |
| Mumps Virus Vaccine Live | Not applicable | 1 year (−20 °C or colder) | 1 year. |
| Normal Horse Serum | 1 year | 2 years | 5 years. |
| Pertussis Vaccine | ......do | Not applicable | 18 months. |
| Pertussis Vaccine Adsorbed | ......do | ......do | Do. |
| Plague Vaccine | ......do | ......do | Do. |
| Plasma products: | |||
| 1. Fresh Frozen Plasma | Not applicable | ......do | 1 year from date of collection of source blood (−18 °C or colder). |
| 2. Liquid Plasma | ......do | ......do | (a) 26 days from date of collection of source blood (between 1 and 6 °C). |
| (b) 40 days from date of collection of source blood only when CPDA-1 solution is used as the anticoagulant (between 1 and 6 °C). | |||
| 3. Plasma | ......do | ......do | 5 years from date of collection of source blood (−18 °C or colder). |
| 4. Platelet Rich Plasma | ......do | ......do | 72 hours from time of collection of source blood, provided labeling recommends storage (20 to 24 °C or between 1 and 6 °C). 5 days if certain approved containers are used (20 to 24 °C). |
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| 5. Source Leukocytes | ......do | ......do | In lieu of expiration date, the collection date shall appear on the label. |
| 6. Source Plasma | ......do | ......do | 10 years (at the recommended storage temperature stated on the label). |
| 7. Therapeutic Exchange Plasma | ......do | ......do | 10 years. |
| Plasma Protein Fraction (Human) | 1 year | ......do | (a) 5 years.(b) 3 years provided labeling recommends storage at room temperature, no warmer than 30 °C). |
| Platelets | Not applicable | ......do | 72 hours from time of collection of source blood, provided labeling recommends storage at 20 to 24 °C or between 1 and 6 °C, or as specified in the directions for use for the blood collecting, processing, and storage system approved for such use by the Director, Center for Biologics Evaluation and Research (CBER). |
| Pneumococcal Vaccine Polyvalent: | |||
| 1. Final bulk powder | ......do | 24 months after potency assay (−20 °C or colder) | Not applicable. |
| 2. Final container | ......do | Not applicable | 2 years (from date of manufacture). |
| Poliovirus Vaccine Inactivated | 1 year | ......do | 1 year. |
| Poliovirus Vaccine Live Oral Trivalent: | |||
| 1. Frozen | Not applicable | 1 year (−10 °C or colder) | 1 year, provided labeling recommends storage at a temperature which will maintain ice continuously in a solid state. |
| 2. Liquid | ......do | Not applicable | 30 days, provided labeling recommends storage between 2 and 8 °C and container has been unopened. |
| Poliovirus Vaccine Live Oral Type I: | |||
| 1. Frozen | ......do | 1 year (−10 °C or colder) | 1 year, provided labeling recommends storage at a temperature which will maintain ice continuously in a solid state. |
| 2. Liquid | ......do | Not applicable | 30 days, provided labeling recommends storage between 2 and 8 °C and container has been unopened. |
| Poliovirus Vaccine Live Oral Type II: | |||
| 1. Frozen | ......do | 1 year (−10 °C or colder) | 1 year, provided labeling recommends storage at a temperature which will maintain ice continuously in a solid state. |
| 2. Liquid | ......do | Not applicable | 30 days, provided labeling recommends storage between 2 and 8 °C and container has been unopened. |
| Poliovirus Vaccine Live Oral Type III: | |||
| 1. Frozen | ......do | 1 year (−10 °C or colder) | 1 year, provided labeling recommends storage at a temperature which will maintain ice continuously in a solid state. |
| 2. Liquid | ......do | Not applicable | 30 days, provided labeling recommends storage between 2 and 8 °C and container has been unopened. |
| Polyvalent bacterial antigens with “No U.S. Standard of Potency” liquid | 1 year | ......do | 18 months. |
| Polyvalent bacterial vaccines with “No U.S. Standard of Potency” liquid | ......do | ......do | Do. |
| Rabies Vaccine: | |||
| 1. Dried | ......do | 2 years | Do. |
| 2. Liquid | 3 months | Not applicable | 6 months. |
| Reagent red blood cells | Not applicable | Not applicable | Thirty-five days from earliest date of collection if kept in liquid form (indefinite storage of reagent red blood cell source material at −65 °C or colder). |
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| ACD Red Blood Cells | ......do | ......do | (a) 21 days from date of collection of source blood, provided labeling recommends storage between 1 and 6 °C and the hermetic seal is not broken during processing.(b) 24 hours after plasma removal, provided labeling recommends storage between 1 and 6 °C and the hermetic seal is broken during processing. |
| CPD Red Blood Cells | ......do | ......do | (a) 21 days from date of collection of source blood, provided labeling recommends storage between 1 and 6 °C and the hermetic seal is not broken during processing.(b) 24 hours after plasma removal, provided labeling recommends storage between 1 and 6 °C and the hermetic seal is broken during processing. |
| CPDA-1 Red Blood Cells | ......do | ......do | (a) 35 days from date of collection of source blood, provided labeling recommends storage between 1 and 6 °C and the hermetic seal is not broken during processing.(b) 24 hours after plasma removal, provided labeling recommends storage between 1 and 6 °C and the hermetic seal is broken during processing. |
| Red Blood Cells Deglycerolized | ......do | ......do | 24 hours after removal from storage at −65 °C or colder, provided labeling recommends storage between 1 and 6 °C, or as specified in the directions for use for the blood collecting, processing, and storage system approved for such use by the Director, CBER. |
| Red Blood Cells Frozen | ......do | ......do | 10 years from date of collection of source blood, provided labeling recommends storage at −65 °C or colder, or as specified in the directions for use for the blood collecting, processing, and storage system approved for such use by the Director, CBER. |
| Rubella and Mumps Virus Vaccine Live | ......do | 1 year (−20 °C or colder) | 1 year. |
| Rubella Virus Vaccine Live | ......do | ......do | Do. |
| Skin Test Antigens for Cellular Hypersensitivity | 6 months | Not applicable | Do. |
| Smallpox Vaccine: | |||
| 1. Liquid | Not applicable | 9 months (−10 °C or colder, if product is maintained as glycerinated or equivalent vaccine in bulk or final containers) | 3 months, provided labeling recommends storage at 0 °C or colder. |
| 2. Dried | 6 months | Not applicable | 18 months. |
| Streptokinase | Not applicable | ......do | Do. |
| Tetanus and Diphtheria Toxoids Adsorbed for Adult Use | 1 year | ......do | 2 years. |
| Tetanus Antitoxin: | |||
| 1. Liquid | ......do | ......do | 5 years with an initial 20 percent excess or potency. |
| 2. Dried | ......do | 2 years | 5 years with an initial 10 percent excess or potency. |
| Tetanus Toxoid | ......do | Not applicable | 2 years. |
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| Tetanus Toxoid Adsorbed | ......do | ......do | Do. |
| Thrombin | ......do | 2 year | 3 years. |
| Thrombin Impregnated Pad | Not applicable | Not applicable | 1 year, or 6 months at 20 to 24 °C. |
| Tuberculin: | |||
| 1. Purified Protein Derivative, diluted | 6 months | ......do | 1 year. |
| 2. Old or Purified Protein Derivative dried on multiple puncture device | 1 year (not to exceed 30 °C; do not refrigerate) | ......do | 2 years, provided labeling recommends storage at a temperature not to exceed 30 °C. Do not refrigerate. |
| 3. Old on multiple puncture device | ......do | ......do | Do. |
| Typhoid Vaccine | 1 year | ......do | 18 months. |
| ACD Whole Blood | Not applicable | ......do | 21 days from date of collection, provided labeling recommends storage between 1 and 6 °C. |
| CPD Whole Blood | ......do | ......do | Do. |
| CPDA-1 Whole Blood | ......do | ......do | 35 days from date of collection, provided labeling recommends storage between 1 and 6 °C. |
| Heparin Whole Blood | ......do | ......do | 48 hours from date of collection, provided labeling recommends storage between 1 and 6 °C. |
| Yellow Fever Vaccine | ......do | 1 year (−20 °C or colder) | 1 year, provided labeling recommends storage at 5 °C or colder. |
(d) Exemptions.
Exemptions or modifications shall be made only upon written approval, in the form of a supplement to the biologics license application, issued by the Director, Center for Biologics Evaluation and Research or the Director of the Center for Drug Evaluation and Research.