3.5 Assembling, Reviewing, and Approving the Analytical Package

• 3.3.1 General Information
• 3.3.2 Worksheet, FD-431
• 3.3.3 Continuation Sheet, FD-431a
• 3.3.4 Miscellaneous Data Entry

3.3.1  General Information

An analyst prepares an analytical package (on FD-431 and FD-431a) or other approved worksheets whenever he or she receives a sample from the sample custodian, transfers an entire sample to a second analyst, or breaks an official seal attached to an analytical package.

3.3.2  Worksheet, FD-431

Complete the FD-431 as follows: (Supplemental to ORA Laboratory Manual, Volume II, Section 2,  ORA-LAB 5.10 Reporting Laboratory Data)

Flags:  Supply a "flag" in the top left margin of the worksheet for samples fitting the categories listed below in order to highlight the nature and significance of the sample for reviewers. This practice emphasizes that there are other related reports or that there is a reporting need. This is an "optional" designation. Laboratories are to follow their local procedures for Flags.

• Check and Additional Analysis Samples;
• Compliance and Surveillance Samples;
• Complaint Samples;
• Follow-up to Consumer Complaints, often denoted "F/U to CC";
• Dealer Holding Samples;
• Split Samples; and
• NDA and ANDA Samples.

Block 1. Product:  Specify the common or usual name of the product received for examination. When a label accompanies the product, the name entered is consistent with the name used on the product label. The name should also be consistent with information reported on the Collection Report. If the product is a drug, include dosage form and strength. If the drug is a USP product, note this as part of the description. 

Block 2. Sample Number:  Enter the FACTS-assigned sample number.

Block 3. Sample Seals:  Check one of the three blocks to show the seal condition upon receipt of the sample. Check "Intact" or "Broken" if the sample is sealed; or "None" if the sample is not sealed.

Block 4. Date Received:  Enter the date the analyst received the sample from the laboratory's Sample Custodian (or other analyst).

Block 5. Received From:  Enter the full name of person (first & last) from whom the sample was received, or the location if the sample was obtained directly from storage.

Block 6. District Or Laboratory:  Enter the common abbreviation for the laboratory (e.g. PRL-SW, DEN-DO).

Block 7. Description Of Sample:  Enter a complete description of the sample received. Quote of the seal inscription (see the next paragraph.) and note condition of the seal if damaged or broken. Quote the collector's identification on the sample, including sub-samples and sub-numbers. Specify the numbers and describe the types of containers (e.g. clear plastic tray within a heat-sealed Mylar bag). Describe any abnormal sample conditions (e.g. torn, broken, not frozen).  The worksheet "description of sample" contains only the basics for sample accountability and is consistent with the information on the Collection Report. Document any discrepancies or deviations found on the worksheet.

Quote the paper seal (FD-415a) exactly as written, including any mistakes and corrections. The seal is quoted in this order: the sample number, date, and printed name (e.g., "X000001 1/1/00  Sidney H. Rogers"). When quoting a metal seal, quote both "U.S. Food and Drug" and the number on the seal. The seal quote is in quotation marks. The seal should be identical to the Collection Report, "Collector's Identification on Seal". If a discrepancy exists, the seal should not be broken and the analyst should notify his or her supervisor. If a seal is completely illegible, the analyst should notify his or her supervisor and resolve seal problems with the investigator before going further.

Quote previously broken seal present (e.g. from a previous analysis). Include "Seals Broken By", initials and date. Do not remove any official seals from sample unless absolutely necessary (e.g. to enter the sample or to maintain the chain of custody when there is no sample reserve). If a seal is removed, mount it on a sheet of heavy mounting paper and include with the analytical package as an attachment. Note the fact that the seal is attached and a brief description as to why the seal was removed on the worksheet in Block 11.

Other Information:  Describe all sample items down to the container in contact with the product. Additionally describe any standards and reagents included with the sample  If there is insufficient space in Block 7, reference location where information is continued. Note in Block 7 any 702(b) portion of sample collected for the claimant.

Block 8. Net Contents:  Record label declaration of net contents. When the net contents are listed in multiple units (i.e., both fluid ounces & milliliters) record both declarations. If the label declares both a "net" and a "drained" weight then record only the net weight.

When applicable, indicate the number of sub-samples examined for net contents in the space to the left of "Units Examined". Also, report the average amount in units as declared on the label.

If there is no label or the label lacks a net contents declaration, check "Not Applicable". If the sample contains a labeled net contents and net contents was not determined, check "Not Determined".

Block 9. Labeling:  Enter the number of original labels, set or copies submitted. Copies may be photocopies, photographs, handwritten copies "verified as true," etc. Copies are identified before copying by the analyst. Check "None"  if no product labels are being included with the analytical package. A "label" may be a single unit such as a paper label surrounding a can, or a set of separate units (e.g. Outer Product Labeling, Immediate Product Labeling, and Package Insert). A set is considered as 1 original.

• Select and submit labeling that includes the sample collector's identification if available. This reinforces sample integrity when an original label cannot be submitted, the analyst identifies the original label and makes copies.
• At least one unit with the original label is retained "as is" for possible court use. Only under exceptional circumstances and with supervisory approval may a label be removed from a single container that represents the sample and be submitted with the worksheet.
• For actionable samples, analytical packages include three (3) sets of labels and labeling or photocopies thereof. Include at least one set of the originals labeling, if available. Three sets of original labeling can be included as long as one unit with the original labeling is retained. Handwritten or typed copies, which are "verified as true" by the original analyst and one additional analyst, may also be submitted. All originals and copies are identified with the FACTS sample number, date and analyst's initials. For non-actionable samples, only one original or copy of the label and labeling need be submitted. In some cases (e.g. survey samples and fresh produce submitted for pesticide residue analysis) submitting labels is not needed. This is at the discretion of the reviewing supervisor.

Attach all labels to a sheet of mounting paper using staples. If labeling is on two sides of submitted article, attach to mounting paper in a manner that allows both sides to be reviewed (e.g. staple just the top or side to the mounting paper). In the top right hand corner of the mounting paper list the sample number, date, analyst's initials and the word "LABELING". Also, at a location on the mounting paper above, below or beside the label, describe what is being submitted (e.g. original cardboard box label, photocopy of bottle labeling, photograph of original tube) and include identification for example as Outer Product Labeling, Immediate Product Labeling, Package Insert. Assemble the labeling set copies as a set in the order packaged.

Block 10. Summary of Analysis:  Summarize in concise and concrete language the following information under the headings and in the order listed:

• Container;
• Labeling;
• Code;
• Product;
• Analysis (Purpose);
• Method; and
• Results

Further clarification of directions for each of these items follows:

Container: Describe any commercial container in immediate contact with the product and any retail container(s) enclosing the immediate container. If a complete container is submitted as labeling, do not describe it here but do state that it is being submitted as labeling. Otherwise, supply details as to the container’s type, size, color, and closure(s). Color and closure may not be pertinent for some products but are always needed for drugs. Describe any abnormalities or unusual conditions associated with the container, such as opened can, abnormal can, evidence of leakage, or broken commercial seal. Do not describe in detail containers furnished by FDA and used by the collector, such as “Inspector's glass vials”, “Whirl-Pak bag”, or “Mason jar”. For NDA and ANDA samples, describe only the primary product container. Secondary materials, such as standards and reagents, need not be described here, but should be referenced in Block 7: Description of Sample.

Examples of container characteristics that should be described include the following:

• Shape (e.g. round, square);
• Color and Transparency (e.g. brown, clear, transparent, translucent, opaque);
• Material (e.g. glass, plastic, Mylar);
• Type (e.g. can, bag, vial, bottle, syringe);
• Closure (e.g. screw cap, septum seal, heat sealed); and
• Dimensions in metric units (e.g. 6.5 cm high x 3.2 cm diameter).

Labeling: Describe all labeling associated with the sample, including that found on retail cartons, inserts, direct printing, and wrappers attached to sample units. If labeling from the outer container enclosing the immediate container is submitted with the Collection Report, the analyst indicates on the worksheet that this labeling has been submitted (e.g. copy of labeling from manufacturer’s box).

Carefully review the label and labeling both for correlation between analytical results and labeling statements and for compliance with applicable labeling regulations. Any discrepancies on the worksheet should be noted, and the reviewing supervisor should reflect these in the summary report.

Code:  Quote sample codes and any product expiration date found on containers.  Identify its type (e.g. embossed, ink stamped, perforated) and cite its location. Do not record manufacturing codes (e.g. UPC, NDC) associated with jars and shipping containers. When there are units with differing codes in the sample, record all the codes and the number of units per code and correlate these with the sample collector's sub-sample numbers. When there is a discrepancy between the observed code(s) and the code(s) cited on the FACTS Collection Report, document the discrepancy on the worksheet. For certain types of samples (e.g. microwave ovens, TVs) a warehouse storage number, serial number, or model number may serve the same function as a product code.

Product:  As applicable, provide a complete and accurate description of the product. Include color, shape, odor, general appearance and texture or consistency in lay language (e.g. frozen shrimp, whole frozen fish). When various sub-samples are raw materials, in-line products, finished products, and environmental samples, describe each in detail. Note any apparent abnormalities of the product (e.g. acetic acid odor in aspirin bottles, broken tablets, discoloration, mold). A picture may be submitted as an attachment to further clarify the product description.

• Do not use the word "normal" to describe a product itself. It may be used to qualify a characteristic of that product, such as "normal appearance". In describing drugs in solid dosage form, the "Identification Guide for Solid Dosage Form", Journal of the American Medical Association (JAMA) provides descriptive terminology that may be helpful. Some products, such as devices, may be difficult to describe. In such cases one may supplement a written description with a drawing or photograph whenever such an illustration will enhance the product description. Identify and attach the illustration and reference it in the written description.

Analysis (Purpose):  Indicate the purpose of the analysis along with the number of units being tested. Note sub-numbers if applicable. Refer to the FACTS Collection Report block entitled "Reason For Collection" if there are questions regarding the purpose. Remember that subsequent reviewers may not be familiar with the details of the case or analysis; therefore, the rationale for a analysis is requested and important.

Method:  For standard methods (e.g. United States Pharmacopeia, National Formulary, Official Methods of Analysis of AOAC INTERNATIONAL) or FDA "Official" methods (e.g. from compendia specified in the Food Drug and Cosmetic Act, Code of Federal Regulations and Compliance Programs, FDA manuals) identify a complete method reference, including edition or date of any revision and page number(s). For computerized references, identify reference with "(on-line)", section or chapter number, date of any revision specific to section or chapter number. Also state any deviation and modifications made to the method. If selection and preparation of the analytical sample is not described in the method or applicable compliance program, describe this information in the analytical package.

For non-standard and laboratory developed methods, the method used is referenced and kept on file with the analyzing laboratory for non-violative samples. For violative samples, the method used is attached to the analytical package. The worksheet references the memo as "attached memo of....". Number and include the memo itself as part of the attachment pages. For more than one sample, this reference is included with the lead sample and reference made to its location noted in the analytical packages for the other samples. Experimental work for validation studies is kept on file with the analyzing laboratory and available upon request.

Results:  Present analytical findings in a clear and concise manner to expedite interpretation of the results, especially by non-technical, non-scientific personnel. Supply units (i.e., mg, oz, nm) for all analytical data and express the data in the same units as those on the product label. Whenever possible, tabulate the analytical data. Also, if sub-samples with differing codes were individually examined, separately report the results for each code because regulatory action may be based on the results for a particular code exclusive of other codes. Results reflect the correct number of significant figures as indicated by the analytical method. Compare the analytical results with the label declarations, published tolerances and standards, regulatory action levels, manufacturer's specifications or other applicable criteria. Set forth clearly any discrepancies between analytical results and labeling statements or other criteria.

For analytical findings that are confirmed directly without a separate check analysis (e.g. confirmation of TLC spots that fade rapidly, identification of isolated filth elements, sensory confirmation) include a signed statement as to what was confirmed and by whom.

Block 11.  Reserve Sample:  When a reserve sample is retained, provide a description of it for accountability purposes. The amount of reserve remaining correlates with the difference between the amount received and the amount used in the analysis, or provide an explanation for any discrepancy.

• Quote the inscription on any new seal placed on the reserve sample. If the reserve sample is not returned to the sample custodian, record the place and condition of storage. When no reserve remains, state "NONE", "NO RESERVE", or something similar. Document the absence of a reserve in FACTS (e.g. on the sample disposition screen).
• When sending a portion of the sample to another party outside the laboratory, describe what was provided, how much, to whom, the date, how it was sealed, and a short explanation as to why the sample was sent.
• If transferring all or a portion of the sample to an analyst within the laboratory  indicate what was provided, to whom, the date, and a brief reason for the transfer.
• Return to the sample custodian any developed x-rays, videotapes, computer records, disks or tapes associated with the sample, which due to their bulk or storage-condition cannot be attached to the worksheet as part of the sample reserve. Otherwise submit such supporting documentation as attachments to the analytical report.

Block 12.  Analyst Signature:  If more than one analyst is involved in the analysis, the worksheet shows "who broke the seal" and the involvement of each individual who assisted with the analytical process. The analyst who broke the seal signs and dates in Block 12a and checks the applicable box. Other analysts, technicians, and aides participating in the analysis also sign in Block 12. Each analyst should identify and initial their work as it appears elsewhere in the package. If more than three individuals are involved in the analysis, the signatures can be continued on the FD-431a or on the back of the worksheet. If an individual's signature is difficult to read, they need to also print their full name adjacent, above, or below to their signature. With computer-generated worksheets the names of the analysts involved may be already entered or typed in this block, and the analyst still needs to sign his or her name.

Block 13.  Worksheet Check:  A second analyst that is fully knowledgeable of the type of analysis performed or supervisor will review the worksheets and supporting records for technical quality (e.g. method suitability, accuracy of calculations, accuracy of data transferred from one section of the worksheet or attachment to another, completeness). The person who performs these checks will sign and date in this block.

Block 14.  Date Reported: Following completion of the worksheet check, enter the date that the completed analytical package is given to the supervisor or reviewing official.

3.3.3  Continuation Sheet, FD-431a

Use the "General Continuation Sheet" to continue information from Block 7, Block 10, Block 11, and to record other data and observations that will not fit on the first page of the worksheet (FD-431). The FD-431a is also used to record raw analytical data, calculations, controls, calibrations, standardizations, and instruments or equipment used.

Complete the blocks of this form as follows:

• Product:  Enter product name identical to that found on the first page of the FD-431.
• Sample No.:  Enter the FACTS assigned sample number. This number should be identical to that on the FD-431.
• Body:  The body on the FD-431a can be used for the following:
  • To continue information from the FD-431. When information is continued on the FD-431a, clearly indicate the block number, name and "continued". Reference where continued in original block on the FD-431.
  • To record raw analytical data, calculations, controls, calibrations, standardization, instrument operating parameters, and identification of instruments or equipment used to complete the analysis.
    
    Use the following guidelines:
    
    
  • Clearly annotate entries. 
  • Enter data in a logical sequence. It is permissible to abbreviate, but there should be sufficient detail and identification for complete reconstruction and understanding of the data.
  • When showing calculations, use the formulas given in the method whenever possible and explain any factors used in the calculation that are not evident in the method or from common knowledge.
  • Provide the name, model number, and instrument identification number on instruments utilized.  If this data is in an attachment, reference the location where this information is found.
  • If the back of the sheet is used, enter the FACTS assigned sample number, date, analyst's initials and page number in the upper right hand corner of each page on which an entry is made.
• Analyst:  The "lead" analyst signs his or her name in this block. When a computer-generated form already has the "lead" analyst's printed name in this block , he or she only needs to initial that entry.
• Page Number:  Consecutively number the pages.

3.3.4  Miscellaneous Data Entry

• Unused areas of  worksheets are marked by lining out. A diagonal line is placed through the entire empty space, initialed, and dated.
• Unused data is lined out, initialed, dated, and state why the data was not used.
• If data generated for a series of similar samples, each under a different sample number, are not completely recorded on or attached to each individual analytical package, reference the lead sample package containing all the original data in each package. Examples of such data include a standard curve, the standardization of a solution, or TLC-plate observations. However, if one of the samples is violative, attach a copy of the original data to that package.Reference the sample number containing the original data on the violative package. Ensure the lead sample containing the original data stays with the violative package. A copy of the original data is not required to be attached to all the sample packages if all of the samples are violative. This reference is included with the lead sample and reference made to its location noted in the analytical packages for the other samples.
• Include full name, source and lot number for all reference standards. List any pertinent preparation conditions (e.g. Drying at 105 °C for two hours, 2.34% water). For working standards include assay value, date, and a reference to where the assay data can be found.
• If a computer program is used to generate results, list the name and date of latest revision. (If it is not shown on the computer-generated sheet.)