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| Other Laboratory Operations Food and Drug Administration |
| DOCUMENT NO.: III-03 | VERSION NO.:1.5 | Section 3 – Recording of Results – Analyst Worksheet | EFFECTIVE DATE: 03/25/2004 | REVISED: 08/11/2008 |
3.5 Assembling, Reviewing, and Approving the Analytical Package
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.)
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