Attachment_19_-_FDA_Form_2481_(Medicated_Feed_Inspection_Report).pdf

FORM FDA 2481 (3/07) Page 1

Department of Health and Human Services Public Health Service

Food and Drug Administration

MEDICATED FEEDS INSPECTION REPORT

DATE OF INSPECTION

FIRM NAME

NAMES OF INSPECTORS

FIRM ADDRESS

ZIP CODE COUNTY

SUMMARY of FINDINGS Summarize the inspection factually and objectively from observations of the condition and practices of the firm.

PSC Graphics (301) 443-1090 EF

FORM FDA 2481 (3/07) Page 2

HISTORY of BUSINESS

1. PARENT FIRM, If applicable (Name / Address) 2. CORPORATE OFFICERS (Name, title, business address)

3. FDA REGISTRATION/LICENSE STATUS

(Check appropriate status)

4. TYPE of FIRM (Check appropriate type)

5. FEED PREPARED FOR

(Check all that apply)

a. Unknown

b. Non-registered

c. Registered (as a drug establishment)

Registration number or FEI:

d. Licensed

License number:

a. Commercial Feed Mill

b. Custom Formula Mixer

c. Mixer-Feeder

d. Other (Please specify)

a. Beef Cattle

b. Dairy Cattle

c. Swine

d. Sheep/Goats

e. Poultry

f. Fish

g. Other (Exotic / Species)

6. VOLUME of BUSINESS

a. Annual tonnage of all MEDICATED feeds manufactured

b. Annual tonnage of all Non-MEDICATED feeds manufactured

7. INTERSTATE BUSINESS

a. Interstate business received? Yes No

b. Interstate business sold? Yes No

If yes, percentage sold? %

RESPONSIBLE PERSONNEL

8. NAME AND TITLE of MOST RESPONSIBLE INDIVIDUAL AT THIS

PLANT TO RECEIVE COPY of REPORT (If more than one person, list)

9. INDICATE TO WHOM FDA FORMS WERE ISSUED (If more than one person, list all)

NOTES: The key CGMP elements are designated on this form with asterisk (**).

Items not covered on this form should be marked with N/C.

Each of the following questions shall be answered. Each “NO” answer shall be explained in the narrative block.

Precede any explanation with appropriate item/question number.

FORM FDA 2481 (3/07) Page 3

Yes No 10. Does firm manufacture feeds containing VFD drugs? If the answer is yes, continue with question 11-15. If the answer is no, skip to item number 16.

Yes No 11. Does the firm distribute VFD feeds to other distributors or manufacturers?

Yes No 12. Has the firm supplied to CVM a written letter of intent to distribute VFD Feeds?

Yes No 13. Are copies of letters of acknowledgement maintained on file at this firm?

14. State the number of VFD orders reviewed during inspection:

Note: If the response is “yes” to any part of item 15 but errors were found in what was observed/provided, please describe and elabo-rate in the narrative section below. Additionally, report in the narrative if firms are found to be operating outside of the VFD approval; for instance, is there evidence that there are other products being used, promoted or handled as VFD drugs? If more than 3 VFD orders are examined, please record findings using additional narrative page(s) or sheets of paper.

15. For the VFD orders reviewed (e.g., up to three in number), did they contain the following information:

a. The name, address and telephone number for the veterinarian and client.

b. Identification of the animals to be treated, including the identification of the species, number of animals, and the specific location of the animals.

c. Date of treatment and, if different, date of prescribing the VFD drug.

d. Name of the animal drug.

e. Level of animal drug in the feed and the amount of feed.

f. Feeding instructions with withdrawal time.

g. Expiration date of the VFD.

h. Any special instructions necessary for use of the drug in conformance with the approval.

i. Required cautionary statements.

j. Number of refills, if permitted by the approval.

k. Signature of the veterinarian.

l. The veterinarian’s license number and the name of the State issuing the license.

m. Other information as required by the individual drug approval.

NARRATIVE

VETERINARY FEED DIRECTIVE (VFD) DRUGS / FEEDS

NARRATIVE

VFD order #1 VFD order #2 VFD order #3

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

Yes No

NARRATIVE

FORM FDA 2481 (3/07)

PERSONNEL (21 CFR 225.10)

Yes No 16. Do the employees involved in the manufacture of medicated feed understand the manufacturing or control functions they perform, including the proper use and location of the equip-ment? For either response (i.e., “yes” or “no”), elaborate in the narrative section.

Yes No 17. Are the employees provided with on-going evaluation and supervision? If yes, include how assessed.

BUILDINGS (21 CFR 225.20)

Yes No 18. Are the grounds of the facility adequately drained and main-tained?

19. In regards to the buildings:

Yes No a. Are they clean, orderly and suitably constructed?

Yes No b. Are the control practices for rodents, birds, insects, and other pests effective?

Yes No c. Do they have facilities to promote personal hygiene?

20. Do the buildings provide adequate space for:

Yes No a. Receipt, inspection, storage, and processing of compo-nents?

Yes No b. Manufacturing, packaging, and labeling of medicated feeds?

Yes No c. Storage of containers, packaging materials, labeling, and products?

Yes No d. Routine maintenance of equipment?

EQUIPMENT (21 CFR 225.30)

21. Describe equipment used for mixing/blending of feeds in the narrative.

22. With regards to assuring the uniformity of medicated feeds:

Yes No a. When installed, was/were the mixer(s)/blender(s) evaluated for their ability to produce feeds of uniform quality?

Yes No b. Since installation, has the firm determined that the mixer’s ability to produce a uniformly mixed feed has not changed?

Explain.

Yes No 23. Has all production equipment, particularly those that are au-tomated and/or computerized, been properly installed and verified to be able to reliably perform as intended?

Yes No 24. Whether manually or by automated means, are drugs ac-curately weighed?

Yes No **25. Are ALL scales and metering devices tested for accuracy upon installation and at least once per year thereafter?

Yes No 26. Is equipment constructed to allow inspection and use of clean-out procedures?

Yes No 27. Is all equipment reasonably clean and properly maintained?

Yes No 28. Is all equipment constructed to prevent contamination with lubricants, coolants, etc.?

FORM FDA 2481 (3/07)

EQUIPMENT (21 CFR 225.30), continued

Yes No 29. Is all equipment of suitable size, design, construction, and precision for the intended purpose?

USE of WORK AND STORAGE AREAS FOR OTHER

PURPOSE (21 CFR 225.35)

Yes No **30. Does the firm avoid storage or handling of toxic or unap-proved feed additives (i.e., fertilizers, herbicides, insecti-cides, rodenticides and pesticides not approved for use in feed) in the same equipment or areas as medicated feeds?

EQUIPMENT CLEANOUT (21 CFR 225.65)

Yes No 31. Do clean out procedures exist for all equipment used in the manufacture and distribution of medicated feeds? If pro-cedures exist, specify the methods, for example: physical, flushing, sequencing, etc.

Yes No **32. Does the clean out procedure appear adequate to prevent unsafe contamination? If no, explain.

Yes No 33. Is there documentation that equipment clean out proce-dures are actually being performed?

34. Describe disposition of clean out material in the narrative.

CONTROL OPERATIONS

Yes No 35. Are feeds stored in a manner to prevent mix-ups with other feeds?

Yes No 36. Is the method of dust control adequate to minimize potential contamination?

37. Is there adequate disposition of:

Yes No a. Spillage?

Yes No b. Leaks?

Yes No c. Broken Bags?

Yes No d. Floor sweepings?

Yes No e. Returns?

Yes No 38. Are drugs used in accordance with their labeled directions, including appropriate species, drug levels, and use?

DRUG COMPONENTS (21 CFR 225.42)

39. Report “DRUG COMPONENTS ON HAND” in self-titled section of this report (page 11).

Yes No **40. Are drugs properly identified, handled and controlled to maintain their integrity and identity?

Yes No 41. Are drugs properly stored? (e.g., Are drugs labeled “Store in a cool, dry place”, or “Store between 32° -81° F”, so stored?)

Yes No 42. Are all drugs within their expiration date?

Yes No 43. Are there RECEIPT RECORDS for incoming lots of drugs?

If yes, answer item 44 a-f below.

FORM FDA 2481 (3/07)

DRUG COMPONENTS (21 CFR 225.42), continued

44. Do the Receipt Records show for each lot of drugs:

Yes No a. Identity and Quantity?

Yes No b. Name of supplier?

Yes No c. Supplier’s lot number or number assigned by the manufacturer

Yes No d. Date received?

Yes No e. Condition of drug received?

Yes No f. Return of damaged goods?

Yes No **45. Is there a DAILY INVENTORY RECORD for each lot of drug (separate from the production record)?

46. Do the Daily Inventory Records for each drug show:

Yes No a. Quantity of drug on hand at beginning and end of the work day?

Yes No b. The amount of each drug used, sold or otherwise disposed of?

Yes No c. The batches or production runs of medicated feed in which each drug was used?

Yes No d. Actions taken to reconcile any discrepancies in the daily inventory record?

**47. Does the firm’s DRUG INVENTORY system:

Yes No a. Make a daily comparison between actual amount of drug used and theoretical drug usage?

Yes No b. Have drug inventory records that agree with calculated us-age?

Yes No c. Include a working definition of what it considers as consti-tuting a significant discrepancy in its drug inventory?

Yes No d. Include procedures for holding feeds on the premises until a significant discrepancy is reconciled?

Yes No 48. Are there any documented significant discrepancies in the firm’s drug inventories? If yes, answer a-b below; If not, skip to item 49.

Yes No a. were documented discrepancies investigated?

Yes No b. was corrective action taken?

Yes No 49. Do the firm’s current drug inventories agree with the amount of drug currently on hand?

Yes No 50. Are all required drug records kept on the premises for at least one year after complete use of a specific lot of drug component?

LABORATORY CONTROLS (21 CFR 225.58)

Yes No **51. Are assays performed on all medicated feeds/manufac-tured according to the schedule specified in CFR 225.58?

Yes No **52. Are investigations performed and appropriate corrective actions taken in response to “out of limits” assay reports?

FORM FDA 2481 (3/07)

LABORATORY CONTROLS (21 CFR 225.58), continued

Yes No 53. Are all investigations documented in writing?

Yes No 54. Are results of assays kept on the premises for not less than one year after distribution of that feed?

Yes No **55. When Category I drugs are assayed and found to be out of limits, are investigations performed?

Yes No 56. Are reports made to CVM of confirmed “out of limits” assays of medicated feeds that have been distributed?

57. Provide the following information on any confirmed “out of limits” results:

a. Name of feed(s) and drug(s) (enter in narrative)

b. Production date or code (enter in narrative)

c. Drug guarantee and assay result (enter in narrative)

LABELING (21 CFR 225.80)

Yes No 58. Does the accompanying labeling (including invoices if used as labeling) include drug level, directions for use and any required withdrawal or warning statements for safe, effective use of the medicated feed?

Yes No 59. Upon receipt from either an outside printer or in-house print shop, are labels and labeling (including placards and pre-printed bags) proofread against the MASTER RECORD FILE to verify their suitability and accuracy?

Yes No 60. Is the proofread label/labeling/pre-printed bag initialed by a responsible individual, dated and kept one year after all labels from that batch have been used?

Yes No **61. Are labels handled and stored in a manner to prevent mixups and periodically reviewed to discard discontinued labels?

**62. Does the firm adequately label the following:

Yes No a. Bagged feeds?

Yes No b. Bulk feeds?

Yes No c. Custom formula feeds?

63. When the firm distributes medicated feed in bag or bulk:

Yes No a. Does complete labeling accompany the shipment?

(Note: The labeling may consist of a placard or other labels attached to the invoice or delivery ticket, or manufacturer’s invoice that identifies the medicated feed and includes adequate information for the use of the medicated feed.)

b. Describe what procedures does the firm use for providing the consignee with labeling upon delivery in the narrative.

MASTER RECORD FILE (21 CFR 225.102)

Yes No 64. Is there a Master Record File or its equivalent for each medicated feed?

**65. Does the Master Record File contain the following for each medicated feed:

Yes No a. Name of medicated feed?

FORM FDA 2481 (3/07)

MASTER RECORD FILE (21 CFR 225.102), continued

65. (Continued)

Yes No b. An accurate formula, including the appropriate levels of drugs and non-drug ingredients under 21 CFR 573 (Food Additives) and 21 CFR 582 (GRAS).

Yes No c. A copy or description of the label or labeling that will ac-company the medicated feeds.

Yes No d. A copy of NADA approved Blue Bird Labeling, or a refer-ence to electronic access to such labeling.

Yes No e. Manufacturing procedures including mixing steps, mix-ing times, assay requirements and the appropriate control directions?

Yes No f. Procedures for estimating quantity produced for bulk feeds?

Yes No 66. Is each Master Record File prepared, checked and signed or initialed by a qualified person?

67. If all or portions of the Master Record File are computerized and/or electronically transmitted from another location, what steps are in place to protect the integrity of the data and signatures?

Describe in the narrative.

Yes No 68. Is each MASTER RECORD FILE kept on the premises for one year after production of the last batch or production run to which it pertains?

PRODUCTION RECORDS (21 CFR 225.102)

69. Is there a production record prepared for each batch or production run of medi-cated feed produced?

Yes No a. Are the records generated/maintained electronically?

Yes No b. Do those records include alarms or error messages that oc-curred during production and any actions taken to clear the error or override the operation of the computer?

**70. Does the production record provide:

Yes No a. A complete and traceable history of the production of a batch or production run?

Yes No b. Product identification?

Yes No c. Date of production?

Yes No d. Written endorsement by a responsible person?

Yes No e. Name and quantity of drug components used?

Yes No f. Theoretical quantity of medicated feed to be produced?

Yes No g. Actual quantity of medicated feed produced?

Yes No 71. Do production records identify specific equipment and bins used in that production if the firm has multiple pieces of the same equipment and multiple bins?

Yes No 72. Are steps in place to minimize mixups, such as running feeds into the wrong bins?

Yes No 73. Does the production formula agree with the formula in the

MASTER RECORD FILE?

FORM FDA 2481 (3/07)

PRODUCTION RECORDS (21 CFR 225.102), continued

Yes No 74. Are production records checked by a responsible individual at the end of the working day to determine that all required production steps have been performed?

75. Mixing:

Provide in the narrative block the:

a. Point in at which drug is added.

b. Mixing time

c. Manner in which mixing is timed.

Yes No 76. Has the firm defined what constitutes a significant discrep-ancy in production? (Including such aspects as theoretical

vs. actual production yield, actual drug usage, etc.)

Yes No 77. Are significant discrepancies immediately investigated and do production records show the corrective actions taken?

Yes No 78. Is an individual batch or production run number, code, date or other suitable identification which permits tracing of the manufacturing history applied to the labeling of the medi-cated feed?

79. Calculate drug levels in a representative number of feeds, and:

a. State the number checked that were right. (In narrative).

b. Report any discrepancies found. Provide evidence of the discrepancy, including formula.

Yes No 80. Is the original, copy, or electronic version of the production record kept on the premises for not less than one year from the date of production?

DISTRIBUTION RECORDS (21 CFR 225.110)

Yes No **81. Does each distribution record provide sufficient information, to relate complaints to specific batches or production runs?

Yes No 82. Are distribution records kept on the premises for not less than one year after the date of shipment?

COMPLAINT FILES (21 CFR 225.115)

Yes No 83. Does the firm have procedures to use as follow-up in re-sponse to product complaints and reports of experiences of product defects?

Yes No 84. Is a file kept for each oral and written complaint or report of product defects? If, yes, does it contain:

Yes No a. Date of complaint?

Yes No b. Complainant’s name and address?

Yes No c. Name and lot or number or date of manufacture of the medicated feed involved?

Yes No d. Specific details of the complaint?

Yes No e. Correspondence, including memoranda of conversations, from the complainant?

Yes No f. Description of all investigations?

Yes No g. Method of disposition of the complaint?

Yes No 85. Are reports of adverse experiences, drug mixups, and other failures of the drug to meet specifications reported as required to CVM?

FORM FDA 2481 (3/07) Page 10

FORM FDA 2481 (3/07) Page 11

DRUG COMPONENTS ON HAND

TRADE NAME DISTRIBUTOR DRUG POTENCY EXPIRATION

DATE

FORM FDA 2481 (3/07) Page 12

Describe in detail all recommendations and warnings given to management and their response to each deviation listed on the FDA 483.

DISCUSSION WITH MANAGEMENT

FDA-2481.indd wwragg

FORM FDA 2481 (3/07)

Department of Health and Human Services Public Health Service Food and Drug Administration

MEDICATED FEEDS INSPECTION REPORT

DATE OF INSPECTION

FIRM NAME

NAMES OF INSPECTORS

FIRM ADDRESS

ZIP CODE

COUNTY

SUMMARY of FINDINGS Summarize the inspection factually and objectively from observations of the condition and practices of the firm.

PSC Graphics (301) 443-1090 EF PSC Graphics (3 0 1) 4 4 3 1 0 9 0 E F

FORM FDA 2481 (3/07)

HISTORY of BUSINESS

1. PARENT FIRM, If applicable (Name / Address)

2. CORPORATE OFFICERS

(Name, title, business address)

3. FDA REGISTRATION/LICENSE STATUS

3. F D A REGISTRATION/LICENSE STATUS

(Check appropriate status)

4. TYPE of FIRM (Check appropriate type)

5. FEED PREPARED FOR

(Check all that apply)

a. Unknown

b. Non-registered

b. Non registered

c. Registered (as a drug establishment) Registration number or FEI:

Registration number or F E I:

d. Licensed License number:

a. Commercial Feed Mill

b. Custom Formula Mixer

c. Mixer-Feeder

c. Mixer Feeder

d. Other (Please specify)

a. Beef Cattle

b. Dairy Cattle

c. Swine

d. Sheep/Goats

e. Poultry

f. Fish

g. Other (Exotic / Species)

6. VOLUME of BUSINESS

a. Annual tonnage of all MEDICATED feeds manufactured

b. Annual tonnage of all Non-MEDICATED feeds

b. Annual tonnage of all Non MEDICATED feeds manufactured

7. INTERSTATE BUSINESS

a. Interstate business received?

Yes No

b. Interstate business sold?

Yes No If yes, percentage sold?

RESPONSIBLE PERSONNEL

8. NAME AND TITLE of MOST RESPONSIBLE INDIVIDUAL AT THIS PLANT TO RECEIVE COPY of REPORT (If more than one person, list)

9. INDICATE TO WHOM FDA FORMS WERE ISSUED

(If more than one person, list all)

NOTES:

The key CGMP elements are designated on this form with asterisk (**).

The key Current Good Manufacturing Practice elements are designated on this form with double asterisks.

Items not covered on this form should be marked with N/C.

Each of the following questions shall be answered. Each “NO” answer shall be explained in the narrative block.

Precede any explanation with appropriate item/question number.

FORM FDA 2481 (3/07)

Yes No

10. Does firm manufacture feeds containing VFD drugs? If the answer is yes, continue with question 11-15. If the answer is answer is yes, continue with questions 11 through 15. If the answer is no, skip to item number 16.

Yes No

11. Does the firm distribute VFD feeds to other distributors or manufacturers?

Yes No

12. Has the firm supplied to CVM a written letter of intent to distribute VFD Feeds?

Yes No

13. Are copies of letters of acknowledgement maintained on file at this firm?

14. State the number of VFD orders reviewed during inspection:

Note: If the response is “yes” to any part of item 15 but errors were found in what was observed/provided, please describe and elabo- rate in the narrative section below. Additionally, report in the narrative if firms are found to be operating outside of the VFD approval; for instance, is there evidence that there are other products being used, promoted or handled as VFD drugs? If more than 3 VFD orders are examined, please record findings using additional narrative page(s) or sheets of paper.

Note: If the response is “yes” to any part of item 15 but errors were found in what was observed/provided, please describe and elaborate in the narrative section below. Additionally, report in the narrative if firms are found to be operating outside of the VFD approval; for instance, is there evidence that there are other products being used, promoted or handled as VFD drugs? If more than 3 VFD orders are examined, please record findings using additional narrative page or pages or sheets of paper.

15. For the VFD orders reviewed (e.g., up to three in number), did they contain the following information:

a. The name, address and telephone number for the veterinarian and client.

b. Identification of the animals to be treated, including the identification of the species, number of animals, and the specific location of the animals.

c. Date of treatment and, if different, date of prescribing the VFD drug.

d. Name of the animal drug.

e. Level of animal drug in the feed and the amount of feed.

f. Feeding instructions with withdrawal time.

g. Expiration date of the VFD.

h. Any special instructions necessary for use of the drug in conformance with the approval.

i.

Required cautionary statements.

j.

Number of refills, if permitted by the approval.

k. Signature of the veterinarian.

l.

The veterinarian’s license number and the name of the State issuing the license.

m. Other information as required by the individual drug approval.

NARRATIVE

VETERINARY FEED DIRECTIVE (VFD) DRUGS / FEEDS

NARRATIVE

VFD order #1 VFD order #2 VFD order #3 Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No

NARRATIVE

FORM FDA 2481 (3/07)

PERSONNEL (21 CFR 225.10)

Yes No

16. Do the employees involved in the manufacture of medicated feed understand the manufacturing or control functions they perform, including the proper use and location of the equip-perform, including the proper use and location of the equipment?

ment? For either response (i.e., “yes” or “no”), elaborate in For either response (i.e., “yes” or “no”), elaborate in the narrative section.

Yes No

17. Are the employees provided with on-going evaluation and

17. Are the employees provided with ongoing evaluation and supervision? If yes, include how assessed.

BUILDINGS (21 CFR 225.20)

Yes No

18. Are the grounds of the facility adequately drained and main-

18. Are the grounds of the facility adequately drained and tained?

maintained?

19. In regards to the buildings:

Yes No

a. Are they clean, orderly and suitably constructed?

Yes No

b. Are the control practices for rodents, birds, insects, and other pests effective?

Yes No

c. Do they have facilities to promote personal hygiene?

20. Do the buildings provide adequate space for:

Yes No

a. Receipt, inspection, storage, and processing of compo-

a. Receipt, inspection, storage, and processing of nents?

components Yes No

b. Manufacturing, packaging, and labeling of medicated feeds?

Yes No

c. Storage of containers, packaging materials, labeling, and products?

Yes No

d. Routine maintenance of equipment?

EQUIPMENT (21 CFR 225.30)

21. Describe equipment used for mixing/blending of feeds in the narrative.

22. With regards to assuring the uniformity of medicated feeds:

Yes No

a. When installed, was/were the mixer(s)/blender(s) evaluated

a. When installed, was or were either the mixer or mixers or blender or blenders evaluated for their ability to produce feeds of uniform quality?

Yes No

b. Since installation, has the firm determined that the mixer’s ability to produce a uniformly mixed feed has not changed?

Explain.

Yes No

23. Has all production equipment, particularly those that are au-

23. Has all production equipment, particularly those that are tomated and/or computerized, been properly installed and automated and/or computerized, been properly installed and verified to be able to reliably perform as intended?

Yes No

24. Whether manually or by automated means, are drugs ac-

24. Whether manually or by automated means, are drugs curately weighed?

accurately weighed?

Yes No **25. Are ALL scales and metering devices tested for accuracy This is a key CGMP element. 25. Are ALL scales and metering devices tested for accuracy upon installation and at least once per year thereafter?

Yes No

26. Is equipment constructed to allow inspection and use of clean-out procedures?

Yes No

27. Is all equipment reasonably clean and properly maintained?

Yes No

28. Is all equipment constructed to prevent contamination with lubricants, coolants, etc.?

NARRATIVE

FORM FDA 2481 (3/07)

EQUIPMENT (21 CFR 225.30), continued Yes No

29. Is all equipment of suitable size, design, construction, and precision for the intended purpose?

USE of WORK AND STORAGE AREAS FOR OTHER

PURPOSE (21 CFR 225.35)

Yes No **30. Does the firm avoid storage or handling of toxic or unap- This is a key CGMP element. 30. Does the firm avoid storage or handling of toxic or proved feed additives (i.e., fertilizers, herbicides, insecti-unapproved feed additives (i.e., fertilizers, herbicides, insecticides, cides, rodenticides and pesticides not approved for use in rodenticides and pesticides not approved for use in feed) in the same equipment or areas as medicated feeds?

EQUIPMENT CLEANOUT (21 CFR 225.65)

Yes No

31. Do clean out procedures exist for all equipment used in the manufacture and distribution of medicated feeds? If pro-manufacture and distribution of medicated feeds? If procedures cedures exist, specify the methods, for example: physical, exist, specify the methods, for example: physical, flushing, sequencing, etc.

Yes No **32. Does the clean out procedure appear adequate to prevent This is a key CGMP element. 32. Does the clean out procedure appear adequate to prevent unsafe contamination? If no, explain.

Yes No

33. Is there documentation that equipment clean out proce-

33. Is there documentation that equipment clean out dures are actually being performed?

procedures are actually being performed?

34. Describe disposition of clean out material in the narrative.

CONTROL OPERATIONS

Yes No

35. Are feeds stored in a manner to prevent mix-ups with other

35. Are feeds stored in a manner to prevent mix ups with other feeds?

Yes No

36. Is the method of dust control adequate to minimize potential contamination?

37. Is there adequate disposition of:

Yes No

a. Spillage?

Yes No

b. Leaks?

Yes No

c. Broken Bags?

Yes No

d. Floor sweepings?

Yes No

e. Returns?

Yes No

38. Are drugs used in accordance with their labeled directions, including appropriate species, drug levels, and use?

DRUG COMPONENTS (21 CFR 225.42)

39. Report “DRUG COMPONENTS ON HAND” in self-titled

39. Report “DRUG COMPONENTS ON HAND” in self titled section of this report (page 11).

Yes No **40. Are drugs properly identified, handled and controlled to This is a key CGMP element. 40. Are drugs properly identified, handled and controlled to maintain their integrity and identity?

Yes No

41. Are drugs properly stored? (e.g., Are drugs labeled “Store in a cool, dry place”, or “Store between 32° -81° F”, so in a cool, dry place”, or “Store between 32° through 81° Farenheit”, so stored?)

Yes No

42. Are all drugs within their expiration date?

Yes No

43. Are there RECEIPT RECORDS for incoming lots of drugs?

If yes, answer item 44 a-f below.

If yes, answer items 44 A through F below.

NARRATIVE

FORM FDA 2481 (3/07)

DRUG COMPONENTS (21 CFR 225.42), continued

44. Do the Receipt Records show for each lot of drugs:

Yes No

a. Identity and Quantity?

Yes No

b. Name of supplier?

Yes No

c. Supplier’s lot number or number assigned by the manufacturer Yes No

d. Date received?

Yes No

e. Condition of drug received?

Yes No

f. Return of damaged goods?

Yes No **45. Is there a DAILY INVENTORY RECORD for each lot of This is a key CGMP element. 45. Is there a DAILY INVENTORY RECORD for each lot of drug (separate from the production record)?

46. Do the Daily Inventory Records for each drug show:

Yes No

a. Quantity of drug on hand at beginning and end of the work A. Quantity of drug on hand at beginning and end of the work day?

Yes No

b. The amount of each drug used, sold or otherwise disposed of?

Yes No

c. The batches or production runs of medicated feed in which each drug was used?

Yes No

d. Actions taken to reconcile any discrepancies in the daily inventory record?

**47. Does the firm’s DRUG INVENTORY system:

This is a key CGMP element. 47. Does the firm’s DRUG INVENTORY system:

Yes No

a. Make a daily comparison between actual amount of drug used and theoretical drug usage?

Yes No

b. Have drug inventory records that agree with calculated us-age?

Yes No

c. Include a working definition of what it considers as consti-tuting a significant discrepancy in its drug inventory?

Yes No

d. Include procedures for holding feeds on the premises until a significant discrepancy is reconciled?

Yes No

48. Are there any documented significant discrepancies in the firm’s drug inventories? If yes, answer a-b below; If not, skip firm’s drug inventories? If yes, answer A and B below; If not, skip to item 49.

Yes No

a. were documented discrepancies investigated?

A. were documented discrepancies investigated?

Yes No

b. was corrective action taken?

Yes No

49. Do the firm’s current drug inventories agree with the amount of drug currently on hand?

Yes No

50. Are all required drug records kept on the premises for at least one year after complete use of a specific lot of drug component?

LABORATORY CONTROLS (21 CFR 225.58)

Yes No **51. Are assays performed on all medicated feeds/manufac- This is a key CGMP element. 51. Are assays performed on all medicated feeds/manufac-tured according to the schedule specified in CFR 225.58?

Yes No **52. Are investigations performed and appropriate corrective This is a key CGMP element. 52. Are investigations performed and appropriate corrective actions taken in response to “out of limits” assay reports?

NARRATIVE

FORM FDA 2481 (3/07)

LABORATORY CONTROLS (21 CFR 225.58), continued Yes No

53. Are all investigations documented in writing?

Yes No

54. Are results of assays kept on the premises for not less than one year after distribution of that feed?

Yes No **55. When Category I drugs are assayed and found to be out of This is a key CGMP element. 55. When Category one drugs are assayed and found to be out of limits, are investigations performed?

Yes No

56. Are reports made to CVM of confirmed “out of limits” assays of medicated feeds that have been distributed?

57. Provide the following information on any confirmed “out of limits” results:

a. Name of feed(s) and drug(s) (enter in narrative)

a. Name of feed or feeds and drug or drugs (narrative).

b. Production date or code (enter in narrative)

c. Drug guarantee and assay result (enter in narrative)

LABELING (21 CFR 225.80)

Yes No

58. Does the accompanying labeling (including invoices if used as labeling) include drug level, directions for use and any required withdrawal or warning statements for safe, effective use of the medicated feed?

Yes No

59. Upon receipt from either an outside printer or in-house

59. Upon receipt from either an outside printer or in house print shop, are labels and labeling (including placards and pre-printed bags) proofread against the MASTER RECORD FILE to verify their suitability and accuracy?

Yes No

60. Is the proofread label/labeling/pre-printed bag initialed by

60. Is the proofread label/labeling/pre printed bag initialed by a responsible individual, dated and kept one year after all labels from that batch have been used?

Yes No **61. Are labels handled and stored in a manner to prevent This is a key CGMP element. 61. Are labels handled and stored in a manner to prevent mixups and periodically reviewed to discard discontinued labels?

**62. Does the firm adequately label the following:

This is a key CGMP element. 62. Does the firm adequately label the following:

Yes No

a. Bagged feeds?

Yes No

b. Bulk feeds?

Yes No

c. Custom formula feeds?

63. When the firm distributes medicated feed in bag or bulk:

Yes No

a. Does complete labeling accompany the shipment?

Note:

The labeling may consist of a placard or other labels attached to the invoice or delivery ticket, or manufacturer’s invoice that identifies the medicated feed and includes adequate information for the use of the medicated feed.)

b. Describe what procedures does the firm use for providing the consignee with labeling upon delivery in the narrative.

MASTER RECORD FILE (21 CFR 225.102)

Yes No

64. Is there a Master Record File or its equivalent for each medicated feed?

**65. Does the Master Record File contain the following for each medicated feed:

This is a key CGMP element. 65. Does the Master Record File contain the following for each medicated feed:

Yes No

a. Name of medicated feed?

NARRATIVE

FORM FDA 2481 (3/07)

MASTER RECORD FILE (21 CFR 225.102), continued

65. (Continued) Yes No

b. An accurate formula, including the appropriate levels of drugs and non-drug ingredients under 21 CFR 573 (Food drugs and non drug ingredients under 21 CFR 573 (Food Additives) and 21 CFR 582 (GRAS).

Additives) and 21 CFR 582 (G R A S).

Yes No

c. A copy or description of the label or labeling that will ac-

c. A copy or description of the label or labeling that will company the medicated feeds.

accompany the medicated feeds.

Yes No

d. A copy of NADA approved Blue Bird Labeling, or a refer-

d. A copy of NADA approved Blue Bird Labeling, or a reference ence to electronic access to such labeling.

to electronic access to such labeling.

Yes No

e. Manufacturing procedures including mixing steps, mix-

e. Manufacturing procedures including mixing steps, mixing ing times, assay requirements and the appropriate control times, assay requirements and the appropriate control directions?

Yes No

f. Procedures for estimating quantity produced for bulk feeds?

Yes No

66. Is each Master Record File prepared, checked and signed or initialed by a qualified person?

67. If all or portions of the Master Record File are computerized and/or electronically transmitted from another location, what steps are in place to protect the integrity of the data and signatures?

Describe in the narrative.

Yes No

68. Is each MASTER RECORD FILE kept on the premises for one year after production of the last batch or production run to which it pertains?

PRODUCTION RECORDS (21 CFR 225.102)

69. Is there a production record prepared for each batch or production run of medi-

69. Is there a production record prepared for each batch or production run of cated feed produced?

medicated feed produced?

Yes No

a. Are the records generated/maintained electronically?

Yes No

b. Do those records include alarms or error messages that oc-

b. do those records include alarms or error messages that curred during production and any actions taken to clear the occurred during production and any actions taken to clear the error or override the operation of the computer?

**70. Does the production record provide:

This is a key CGMP element. 70. Does the production record provide:

Yes No

a. A complete and traceable history of the production of a batch or production run?

Yes No

b. Product identification?

Yes No

c. Date of production?

Yes No

d. Written endorsement by a responsible person?

Yes No

e. Name and quantity of drug components used?

Yes No

f. Theoretical quantity of medicated feed to be produced?

Yes No

g. Actual quantity of medicated feed produced?

Yes No

71. Do production records identify specific equipment and bins used in that production if the firm has multiple pieces of the same equipment and multiple bins?

Yes No

72. Are steps in place to minimize mixups, such as running feeds into the wrong bins?

Yes No

73. Does the production formula agree with the formula in the

MASTER RECORD FILE?

NARRATIVE

FORM FDA 2481 (3/07)

PRODUCTION RECORDS (21 CFR 225.102), continued Yes No

74. Are production records checked by a responsible individual at the end of the working day to determine that all required production steps have been performed?

75. Mixing:

Provide in the narrative block the:

a. Point in at which drug is added.

b. Mixing time

c. Manner in which mixing is timed.

Yes No

76. Has the firm defined what constitutes a significant discrep-

76. Has the firm defined what constitutes a significant discrepancy ancy in production? (Including such aspects as theoretical in production? (Including such aspects as theoretical

vs. actual production yield, actual drug usage, etc.)

Yes No

77. Are significant discrepancies immediately investigated and do production records show the corrective actions taken?

Yes No

78. Is an individual batch or production run number, code, date or other suitable identification which permits tracing of the manufacturing history applied to the labeling of the medi-manufacturing history applied to the labeling of the cated feed?

medicated feed?

79.

Calculate drug levels in a representative number of feeds, and:

a. State the number checked that were right. (In narrative).

b. Report any discrepancies found. Provide evidence of the discrepancy, including formula.

Yes No

80. Is the original, copy, or electronic version of the production record kept on the premises for not less than one year from the date of production?

DISTRIBUTION RECORDS (21 CFR 225.110)

Yes No **81. Does each distribution record provide sufficient information, This is a key CGMP element. 81. Does each distribution record provide sufficient information, to relate complaints to specific batches or production runs?

Yes No

82. Are distribution records kept on the premises for not less than one year after the date of shipment?

COMPLAINT FILES (21 CFR 225.115)

Yes No

83. Does the firm have procedures to use as follow-up in re-

83. Does the firm have procedures to use as follow up in response sponse to product complaints and reports of experiences of to product complaints and reports of experiences of product defects?

Yes No

84. Is a file kept for each oral and written complaint or report of product defects? If, yes, does it contain:

Yes No

a. Date of complaint?

A. Date of complaint?

Yes No

b. Complainant’s name and address?

Yes No

c. Name and lot or number or date of manufacture of the medicated feed involved?

Yes No

d. Specific details of the complaint?

Yes No

e. Correspondence, including memoranda of conversations, from the complainant?

Yes No

f. Description of all investigations?

Yes No

g. Method of disposition of the complaint?

Yes No

85. Are reports of adverse experiences, drug mixups, and other failures of the drug to meet specifications reported as required to CVM?

FORM FDA 2481 (3/07)

NARRATIVE

FORM FDA 2481 (3/07)

DRUG COMPONENTS ON HAND

TRADE NAME

DISTRIBUTOR

DRUG

POTENCY

EXPIRATION

DATE

FORM FDA 2481 (3/07)

Describe in detail all recommendations and warnings given to management and their response to each deviation listed on the FDA 483.

DISCUSSION WITH MANAGEMENT