**Draft Outline for Positron Emission Tomography (PET) GMPs**

**Working Draft**

**Not for Implementation**

**February 1999**

**This document is a preliminary working draft prepared by the Agency as
a starting point for discussions. It does not reflect the official
Agency position on CGMPs for PET products and may not be used to satisfy
regulatory requirements.**

Table of Contents

I. Scope [3](#i.-scope)

II\. Quality System [3](#ii.-quality-system)

III\. Laboratory Controls [5](#iii.-laboratory-controls)

IV\. Production and Process Controls
[7](#iv.-production-and-process-controls)

V. Control of Components and Drug Product Containers and Closures
[10](#v.-control-of-components-and-drug-product-containers-and-closures)

VI\. In-Process and Finished Product Acceptance Activities
[12](#vi.-in-process-and-finished-product-acceptance-activities)

VII\. Nonconforming PET Drug Product and Corrective and Preventive
Action
[14](#vii.-nonconforming-pet-drug-product-and-corrective-and-preventive-action)

VIII.Labeling and Packaging Control
[15](#viii.-labeling-and-packaging-control)

IX\. Storage and Distribution [15](#ix.-storage-and-distribution)

X. Records [16](#x.-records)

XI\. Returned and Salvaged Drug Products
[18](#xi.-returned-and-salvaged-drug-products)

DEFINITIONS [20](#definitions)

**Draft Outline for Positron Emission Tomography (PET) CGMPs**

# I. Scope

Minimum current good manufacturing practice for methods to be used in,
and the facilities and controls used for the production, holding, or
distribution of a safe and effective positron emission tomography (PET)
drug intended for human use.

# II. Quality System 

1\. Each PET Center must establish, implement and maintain a quality
system that has the following features: organizational structure;
defined responsibilities; and allocation of resources.

2.  Review suitability and effectiveness of the quality system at
    defined intervals and with sufficient frequency according to
    established procedures to ensure that the quality system satisfies
    the requirements and the established quality policy and objectives.

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3.  Dates and results of quality system reviews must be documented.

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4.  Quality system must include a quality control unit.

-   With responsibility and authority to approve or reject all
    components, drug product containers, closures, in‑process materials,
    packaging material, labeling, and PET drug products.

-   Responsible for approving or rejecting all procedures or
    specifications affecting the identity, strength, quality, and purity
    of the drug product.

-   Authority to review production records to ensure that no errors have
    occurred or, if errors have occurred, that they have been fully
    investigated and corrective action has been taken.

-   Responsible for approving or rejecting drug products produced under
    contract by another company.

-   Has adequate laboratory facilities available for the testing and
    approval (or rejection) of components, drug product containers,
    closures, packaging materials, in‑process materials, and drug
    products.

-   Responsibilities and procedures applicable to the quality control
    unit must be in writing; such written procedures must be followed.

5.  Quality audits performed to ensure that the quality system is in
    compliance with the established quality system requirements and to
    determine the effectiveness of the quality system.

-   Conduct quality audits according to pre-determined frequency.

-   Conducted by individuals who do not have direct responsibility for
    the matters being audited.

-   Corrective action(s), including a reaudit of deficient matters, must
    be taken when necessary.

-   Report results of each quality audit, and reaudit(s) where taken,
    and have reports reviewed by a manager having responsibility for the
    matters audited.

-   Manager of the PET center must certify in writing that the quality
    audits have been performed and documented, and must state the dates
    on which reviews and audits were performed and whether any required
    corrective action has been undertaken. Actual results need not be
    shown to FDA.

6.  The quality system must ensure that the PET center has a sufficient
    number of personnel for the production, holding, storage, testing,
    and distribution of a safe and effective PET drug with the necessary
    education, background, training, and experience to enable them to
    perform their assigned functions correctly.

# III. Laboratory Controls

1.  Specifications, standards, sampling plans, test procedures, or other
    laboratory controls to be drafted by the appropriate organizational
    unit and reviewed and approved by the quality control unit.

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2.  These requirements to be followed and documented at the time of
    performance. Deviations from the written specifications, standards,
    sampling plans, test procedures, or other laboratory control
    mechanisms must be recorded and justified.

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3.  Laboratory controls to include the establishment of

scientifically sound and appropriate specifications, standards,

sampling plans, and test procedures designed to ensure that

components, drug product containers, closures, in‑process materials, and
drug products conform to appropriate standards of identity, strength,
quality, and purity.

4.  Each PET center ensures that all measuring gauges, recording devices
    and test equipment, including mechanical, automated, or electronic
    test equipment, is suitable for intended purposes and capable of
    producing valid results. Procedures to ensure that Each PET center
    ensures that all measuring gauges, recording equipment is routinely
    calibrated, inspected, checked, and maintained must be established
    and followed. Activities to be documented.

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5.  Calibration procedures to include specific directions and limits for
    accuracy, sensitivity, specificity, precision and reproducibility of
    performance.

-   When limits are not met, there must be provisions for remedial
    action to reestablish the limits and to evaluate whether there was
    any adverse effect on the identity, strength, quality, and purity of
    the PET drug.

-   Instruments and equipment not meeting established calibration
    criteria must not be used. Activities are to be documented.

-   Calibration standards used for measuring and testing equipment must
    be traceable to national or international standards, if available,
    or to an internal reproducible standard established to maintain
    consistency.

-   The equipment identification, calibration dates, the individual
    performing each calibration, and the next calibration date must be
    documented. These records must be readily available to the personnel
    using such equipment and to the individuals responsible for
    calibrating the equipment.

6\. Laboratory records to include complete data derived

from all tests necessary to ensure compliance with established

specifications and standards, including examinations and assays,

as follows:

-   A description of the sample received for testing with identification
    of the source (that is, the location where the sample was obtained),
    quantity, lot number or other distinctive code, time and date sample
    was taken, and time and date the sample was received for testing.

-   A statement of each method used in the testing of the sample to
    indicate the location of data establishing that the methods used in
    the testing of the sample meet proper standards of accuracy and
    reliability as applied to the product tested.

-   The suitability of all testing methods used must be verified under
    actual conditions of use.

7\. A statement of the weight or measure of the sample used for

each test.

8\. A complete record of all data obtained in the course of

each test, including all graphs, charts, and spectra from laboratory
instrumentation, properly identified to show the specific component,
drug product container, closure, in‑process material, or drug product
for each lot tested.

9\. A record of all calculations performed in connection with

each test, including units of measure, conversion factors, and

equivalency factors.

10\. A statement of the results of tests and how the results

compare with established standards of identity, strength, quality, and
purity for the component, drug product container, closure, in‑process
material, or drug product tested.

11\. The initials or signature of the person who performs each

test and the date(s) the tests were performed. Documentation showing
that the original records have been reviewed for accuracy, completeness,
and compliance with established standards.

12\. Complete records must be maintained of any modification

of an established method employed in testing. Records to

include the reason for the modification and data to verify that

the modification produced results that are at least as accurate

and reliable for the material being tested as the established

method.

13\. Complete records must be maintained of any testing and

standardization of laboratory reference standards, reagents,

and standard solutions.

# IV. Production and Process Controls

1\. Each PET center to ensure that key process parameters that could
affect product quality are controlled and monitored. Develop and follow
written production and process control procedures. The PET center to
document that key process parameters were controlled in accordance with
procedures at the time of performance. Deviations from the written
procedures to be recorded and justified.

2*.* Each PET center to establish, maintain, and follow procedures for
changes to a specification, method, process, or procedure. Changes to be
validated before implementation, and activities documented.

3\. Each PET center to establish, maintain, and follow procedures to
adequately control environmental conditions, where necessary.
Environmental control system(s) must be periodically inspected to verify
that the system, including necessary equipment, is adequate and
functioning properly. Activities to be documented and reviewed.

4\. Each PET center to establish, maintain, and follow procedures to
prevent contamination of equipment or product by substances or personnel
that could reasonably be expected to have an adverse effect on product
quality.

5\. PET production facilities to be of suitable design and contain
sufficient space to perform necessary operations, prevent mixups, and
assure orderly handling of materials and equipment.

6\. Each PET center must ensure that all equipment used in the
production process is appropriately designed, constructed, placed, and
installed for its intended use. Equipment must be constructed so that
surfaces that contact components, in‑process materials, or drug products
are not reactive, additive, or absorptive so as to alter the quality of
the drug product beyond the official or other established requirements.

7\. Each PET center to establish, maintain, and follow appropriate
schedules for the adjustment, cleaning, and other maintenance of
equipment to ensure proper functioning of equipment. Maintenance
activities, including the date and individual(s) performing the
activities, must be documented.

8\. Computers or automated data processing systems used as part of
production must be validated for their intended use according to an
established protocol. Automated data processing system changes must be
reviewed to determine the need for revalidation before approval and
issuance. Validation activities and results to be documented.

9\. Actual yields and percentages of theoretical yield must be

determined at the conclusion of each appropriate phase of production or
holding of a PET drug.

10\. The manufacturing process must be validated according to
established procedures, and the quality control unit must approve the
validation. The validation activities and results, including the date
and signature(s) of the individual(s) approving the validation, the
monitoring and control methods and data, and the major equipment
qualified, must be documented.

11\. When changes or process deviations occur, the PET center must
review and evaluate the changed process and perform revalidation.
Activities to be documented.

12\. Each PET center must establish, maintain, and follow written
procedures that will assure that the complete history of the production
and distribution of PET drugs can be determined. This may be done by
identifying with a control number each batch or portion of a batch of
PET drugs and documenting this number in the batch production and
control record. The procedures must facilitate corrective action in the
event that defective product quality is identified.

13\. Batch production and control records must be prepared for

each batch of drug product produced and must include complete

information relating to the production and control of each batch. These
records must include:

-   An accurate reproduction of the appropriate master production or
    control record, checked for accuracy, dated, and signed;

-   Documentation that each significant step in the production or
    holding of the batch was accomplished, including:

1.  Dates

2.  Identity of individual and major equipment used;

3.  Specific identification of each batch of component or in‑process
    material used;

4.  Weights and measures of components used in the course of production;

5.  In‑process and laboratory control results;

6.  A statement of the actual yield and a statement of the percentage of
    theoretical yield at appropriate phases of processing;

7.  Specimens or copies of all labeling used;

8.  A description of drug product containers and closures;

9.  Any sampling performed;

10. Names of persons performing and directly supervising or checking
    each significant step in the operation;

11. Any investigation made into the failure of a batch or any of its
    components to meet any of its specifications.

14\. All drug product production and control records, including

those for packaging and labeling, must be reviewed and approved

to determine compliance with all established, approved written
procedures before a batch is released for administration to a patient.
This review and approval must be documented.

15\. Any unexplained discrepancy or the failure of a batch or any of its
components to meet any of its specifications must be thoroughly
investigated, whether or not the batch has already been distributed. The
investigation must extend to other batches of the same drug product and
other drug products that may have been associated with the specific
failure or discrepancy. A written record of the investigation must be
made and maintained and must include the conclusions, follow-up, and a
description of any corrective action.

# V. Control of Components and Drug Product Containers and Closures

1\. Each PET center must establish, maintain, and follow written
procedures describing in sufficient detail the receipt, identification,
storage, handling, sampling, testing, and approval or rejection of
components and drug product

containers and closures.

2\. Components and drug product containers and closures must

be handled and stored at all times in a manner to prevent contamination
and/or deterioration. Containers and closures includes the dispensing
and administration assemblies.

3\. Each component and container or grouping of containers and closures
for the drug product must be uniquely identified for each lot in each
shipment received. This identifier must be used to trace the disposition
of each lot. Each lot must be appropriately marked to reflect its status
(i.e., quarantined, approved, or rejected).

4\. Upon receipt and before acceptance, each container or grouping of
containers of components, drug product containers, and closures must be
examined visually for appropriate labeling as to contents, container
damage, broken seals, and contamination.

5\. Components, drug product containers, and closures must

be stored under quarantine until they have been tested or examined, as
appropriate, and released.

6\. Each lot of components, drug product containers, and closures must
be withheld from use until the lot has been sampled, tested, or
examined, as appropriate, and released for use by the quality control
unit.

7\. Representative samples of each shipment of each lot must

be collected for testing or examination. Samples must be collected in a
manner to prevent contamination of either the component or the sample.
Samples must be examined and tested as follows:

-   At least one test must be conducted to verify the identity of each
    component of a drug product. Specific identity tests, if they exist,
    must be used.

-   Each component must be tested for conformity with all appropriate
    written specifications for purity, strength, and quality. In lieu of
    such testing, a report of analysis may be accepted from the supplier
    of a component, provided that at least one specific identity test is
    conducted on such component by the PET center, and provided that the
    PET center establishes the reliability of the supplier\'s analyses.

-   Containers and closures must be tested for conformance with
    specifications. In lieu of such testing by the PET center, a
    certificate of testing may be accepted from the supplier, provided
    that at least a visual identification is conducted on such
    containers/closures by the PET center and provided that the PET
    center establishes the reliability of the supplier\'s test results.

-   Each lot of a component, drug product container, or closure that is
    susceptible to objectionable microbiological contamination must be
    examined against established specifications for such contamination.

8\. Any lot of components, drug product containers, or closures

that meets the appropriate written specifications of identity,

strength, quality, and purity may be approved and released for use. Any
lot of such material that does not meet such specifications must be
rejected.

9\. Components, drug product containers, and closures may be retested or
reexamined for identity, strength, quality, and purity as necessary,
e.g., after storage for long periods or after exposure to air, heat, or
other conditions that might adversely affect the component, drug product
container, or closure, if the PET center wants to use the components,
drug product containers, or closures. After retesting or reexamination,
the components, drug product containers, and closures must be approved
or rejected by the quality control unit.

10\. Rejected components, drug product containers, and closures

must be discarded.

11\. Drug product containers and closures must not be reactive,

additive, or absorptive, and must be sterile, pyrogen-free, and protect
the drug product so as to preserve its established safety, identity,
strength, quality, and purity.

12\. Records for components, drug product containers, and closures must
include the following:

-   The identity and quantity of each shipment of each lot of
    components, drug product containers, and closures; the name of the
    supplier; the supplier\'s lot number(s) if known; the unique
    identifier for that lot; and the date of receipt. The name and
    location of the prime manufacturer, if different from the supplier,
    must be listed if known.

-   The results of any test or examination performed and resulting
    actions.

-   The disposition of rejected components, drug product containers, and
    closures.

# VI. In-Process and Finished Product Acceptance Activities

1.  Each PET center must establish, maintain, and follow procedures for
    acceptance activities including inspections, tests, or other
    verification activities. These procedures must be established,
    maintained, and followed.

2\. Each PET center must ensure that specified requirements for
in‑process materials are established, maintained, and followed.
Procedures must ensure that in‑process materials are controlled until
the required tests or other verification activities have been completed,
or necessary approvals are received, and are documented.

3.  Each PET center must ensure that each PET drug product batch meets
    the established acceptance criteria.

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4.  PET drug products must be held in quarantine or otherwise adequately
    controlled until released and must not be released for distribution
    until the following occur:

-   Associated data and documentation are reviewed;

-   Release is authorized by the signature(s) of a designated
    individual(s); and

-   Authorization is dated.

5\. Each PET center must document acceptance activities. Records must
include: acceptance activities performed; dates the activities are
performed; the results; the signature(s) of the individual(s) conducting
the acceptance activities; and the equipment used. These records must be
part of the Historical Record.

6\. Each PET center must identify by suitable means the acceptance
status of the PET drug product, i.e., its conformance or nonconformance
with acceptance criteria. The identification of acceptance status must
be maintained throughout production of the product to ensure that only a
product that has passed the required acceptance activities is
distributed or used.

7\. For each batch of drug product, there must be appropriate

laboratory determination of satisfactory conformance to acceptance
criteria for the drug product, including its identity, strength,
quality, and purity, prior to administration to the patient. This does
not include sterility testing, which does not need to be completed
before administration to the patient but should be completed as soon as
possible after filtration.

8\. When the product is distributed prior to completion of testing,
there must be a mechanism to inform the receiving facility of final
product test results before the drug is administered to the patient.
Such communication with the receiving facility must be documented. If
the product fails the sterility tests, these results must be
communicated to the receiving facility.

9.  Any sampling and testing plans must be described and conducted in
    accordance with written procedures.

10\. The accuracy, sensitivity, specificity, and reproducibility

of test methods must be established and documented.

11\. Drug products failing to meet established standards or

specifications and any other relevant quality control criteria

must be rejected. Reprocessing may be performed. Prior to acceptance and
use, reprocessed material must meet appropriate standards,
specifications, and any other relevant criteria.

# VII. Nonconforming PET Drug Product and Corrective and Preventive Action

1.  Each PET center must establish, maintain and follow procedures to
    control a PET drug product that does not conform to specified
    requirements. The procedures must address the identification,
    documentation, evaluation, segregation, and disposition of
    nonconforming product and the need for an investigation and
    notification of the quality control unit.

2\. Each PET center must establish, maintain, and follow procedures for
implementing corrective and preventive action as follows:

-   Analyzing processes, work operations, quality audit reports, quality
    records, complaints, returned product, and other sources of quality
    data to identify existing and potential causes of nonconforming
    product, or other quality problems.

-   Investigating the cause of nonconformities relating to product,
    processes, and the quality system.

-   Identifying the action(s) needed to correct and prevent recurrence
    of nonconforming product and other quality problems. Verify or
    validate that the corrective action is effective and does not
    adversely affect the PET drug.

-   Implementing and recording changes in methods and procedures needed
    to correct and prevent identified quality problems. Ensure that the
    information related to the problem is disseminated to those directly
    responsible for ensuring the quality of the PET drug.

# VIII. Labeling and Packaging Control

1\. Labels must be legible and applied so as to remain legible and
affixed during the customary conditions of processing, storage,
handling, distribution, and use.

2\. Labeling and packaging operations must be controlled to prevent
labeling and product mixups. The label and labeling used for each
production unit, lot, or batch must be documented in the Historical
Record.

3\. A required control number must be on the label or must accompany the
PET drug through distribution.

4\. The examination and review of labels and labeling for conformity
with established specifications must be documented. A copy of each label
must be affixed to each batch production record.

5\. Each PET center must ensure that packaging and shipping containers
are designed and constructed to protect against alteration or damage
during the customary conditions of storage, handling, distribution, and
use.

6\. To ensure that a PET drug product meets applicable standards

of identity, strength, quality, and purity at the time of use,

it must bear on its label an expiration date and time determined by
appropriate stability testing.

7\. A written testing program must be established and implemented that
is designed to assess the stability characteristics of PET drug
products. The results of such stability testing must be documented and
used in determining appropriate storage conditions and expiration dates
and times. The program must establish storage conditions for stability
samples as well as reliable, meaningful, and specific test methods.

# IX. Storage and Distribution 

1\. Procedures must be established, maintained, and followed for the
control of products to prevent mixups, damage, deterioration,
contamination, or other adverse effects pending use or distribution and
to ensure that no obsolete, rejected, or deteriorated product is used or
distributed. Procedures must be established, maintained, and followed
that describe the methods for authorizing receipt from and dispatch for
distribution.

2.  Each PET center must establish, maintain, and follow procedures for
    control and distribution of PET drug products being shipped from the
    PET center to ensure that only those products approved for release
    are distributed, that purchase orders are reviewed to ensure that
    ambiguities and errors are resolved before release and that the
    process of shipping does not adversely affect the product.

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3.  Where fitness for use or quality deteriorates over time, the
    procedures must ensure that lots which have deteriorated beyond
    acceptable fitness for use are not distributed or administered to
    the patient.

4\. Distribution records must be maintained that include or refer to the
location of:

-   The name and address of the initial consignee;

-   The identification and quantity of PET drugs shipped;

-   The date and time shipped; and

-   Any control number(s) used.

# X. Records

1\. All records must be maintained at the PET center or other location
that is reasonably accessible to responsible officials of the PET center
and to employees of FDA designated to perform inspections. Such records,
including those not stored at the inspected establishment, must be made
readily available for review and copying by FDA employees. Records must
be legible and must be stored to minimize deterioration and to prevent
loss. Back-up copies must be made of those records stored in automated
data processing systems.

2\. Records deemed confidential by the PET center may be marked to aid
FDA in determining whether information may be disclosed under the public
information regulations.

3.  All required records must be retained for a period of no less than 3
    years from the date of release of the PET drug product.

4\. To ensure uniformity from batch to batch, master production

and control records for each drug product (these are created before
production starts), including each batch size of each drug product, must
be prepared, dated, and signed by one person and independently checked,
dated, and signed by a second person. The preparation of master
production and control records must be described in a written procedure
and such written procedure must be followed.

5\. Master production and control records must include:

-   The name and strength and dosage form;

-   The name and weight or measure of each active ingredient per dosage
    unit or per unit of weight or measure of the drug product, and a
    statement of the total weight or measure of any dosage unit;

-   A complete list of components designated by names or codes
    sufficiently specific to indicate any special quality
    characteristic;

-   An accurate statement of the weight or measure of each component,
    using the same weight system (metric, avoirdupois, or apothecary)
    for each component. Reasonable variations may be permitted, however,
    in the amount of components necessary for preparation of the dosage
    form, provided they are justified in the master production and
    control records;

-   A statement of theoretical yield, including the maximum and minimum
    percentages of theoretical yield beyond which investigation is
    required;

-   A description of the drug product containers, closures, and
    packaging materials, including a specimen or copy of each label and
    all other labeling;

-   Complete manufacturing and control instructions, sampling and
    testing procedures, specifications, special notations, and
    precautions to be followed.

6.  Each PET center must establish, maintain, and follow procedures to
    ensure that a historical record for each batch, lot, or unit is
    maintained to demonstrate that production and holding of the PET
    drug was in accordance with the requirements.

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7.  The historical record must include, or refer to the location of, the
    dates of manufacture, the quantity manufactured and/or vial size,
    the acceptance records, the labeling, and any control, batch, or lot
    number used.

8\. Written procedures describing the handling of all complaints
regarding a drug product must be established, maintained, and followed.
Such procedures must include provisions for review by the quality
control unit of any complaint involving the possible failure of a drug
product to meet any of its specifications and a determination as to the
need for an investigation. Such procedures must include provisions for
review to determine whether the complaint represents a serious and
unexpected adverse drug experience that must be reported to the Food and
Drug Administration.

9\. A written record of each complaint must be maintained

in a file designated for drug product complaints. The file regarding
such drug product complaints must be maintained at the establishment
where the drug product involved was manufactured, processed, or packed,
or such file may be maintained at another facility if the written
records in such files are readily available for inspection at that other
facility.

10\. The written record must include the following information,

where known: name and strength of the drug product, lot

number, name of complainant, nature of complaint, and reply

to complainant.

11\. When an investigation is conducted, the written record must include
the findings of the investigation and follow-up. The record or copy of
the record of the investigation must be maintained at the establishment
where the investigation occurred.

12\. Where an investigation is not conducted, the written record must
include the reason that an investigation was found not to be necessary
and the name of the responsible person making such a determination.

# XI. Returned and Salvaged Drug Products

1\. Returned products must be identified as such and destroyed. A
returned PET drug product must not be reprocessed.

2\. PET drug products that have been subjected to improper storage
conditions including extremes in temperature, humidity, smoke, fumes,
pressure, age, or radiation due to natural disasters, fires, accidents,
or equipment failures must not be salvaged and returned to the
marketplace.

# DEFINITIONS

\(a\) *Acceptance criteria* means numerical limits, ranges, or other
criteria for tests that are used for or in making a decision to accept
or reject a unit, lot, or batch (or any other subgroups of manufactured
units).

\(b\) *Act* means the Federal Food, Drug, and Cosmetic Act, as amended
(21 U.S.C. 301 et seq.).

\(c\) *Actual yield* means the quantity that is actually produced at any
appropriate phase of manufacture, processing, or packing of a particular
drug product.

\(d\) *Batch* means a specific quantity of a PET drug or other material
that is intended to have uniform character and quality, within specified
limits, and is produced according to a single manufacturing order during
the same cycle of manufacture.

\(e\) *Complaint* means any communication that alleges deficiencies
related to the identity, strength, quality, or purity of a PET drug
after it is released for distribution.

*(*f*) Component* means any ingredient intended for use in the
production of a PET drug, including ingredients that may not appear in
the final drug product.

\(g\) *Drug product* means finished dosage form that contains a PET
drug, generally, but not necessarily in association with one or more
other ingredients.

\(h\) *Historical record* means a compilation of records containing the
production history of a PET drug.

\(i\) *Lot* means a batch, or a specific identified portion of a batch,
having uniform character and quality within specified limits; or, in the
case of a PET drug product produced by continuous process, it is a
specific identified amount produced in a unit of time or a quantity
produced in a manner that assures its having uniform character and
quality within specified limits.

*(j*) *Lot number, control number, or batch number* means any
distinctive combination of letters, numbers, or symbols, from which the
complete history of the compounding, manufacturing, processing, packing,
holding, and distribution of a batch or lot of PET drug product, or
target material used specifically in the preparation of PET drugs, can
be determined.

\(k\) *Manager* means an employee of a PET center who has authority to
establish or make changes to the quality policy and quality system.

\(l\) *Master production and control record* means a compilation of
records containing the procedures and specifications for a PET drug.

\(m\) *Nonconformity* means the failure to meet a specified requirement.

\(n\) *Percentage of theoretical yield* means the ratio of the actual
yield (at any appropriate phase of production of a particular drug
product) to the theoretical yield (at the same phase), stated as a
percentage.

\(o\) *PET center* means any person(s) who engages in the production
and/or distribution of a PET drug for use in humans.

\(p\) *Positron Emission Tomography (PET) drug* means a drug that
exhibits spontaneous disintegration of unstable nuclei by the emission
of positrons and is used for the purpose of providing dual photons
present in a finished dosage form.

\(q\) *Potency* is the activity of the drug product as indicated by
appropriate laboratory tests or by adequately developed and controlled
clinical data (expressed, for example, in terms of units by reference to
a standard).

\(r\) *Process validation* means establishing by objective documented
evidence that a process consistently produces a result or product
meeting its predetermined specifications.

\(s\) *Production* means the compounding, manufacturing, processing,
packaging, and/or labelng of a PET drug.

\(t\) *Quality audit* means a systematic examination of a quality system
that is performed at defined intervals and at sufficient frequency to
determine whether both quality system activities and the results of such
activities comply with quality system procedures, that these procedures
are implemented effectively, and that these procedures are suitable to
achieve quality system objectives.

\(u\) *Quality control unit* means any person or organizational element
designated by an organization to be responsible for the duties relating
to quality control.

*(v) Quality policy* means the overall commitment of the organization
with respect to the *quality system*, as established by a manager.

\(w\) *Quality system* means organizational structure, defined
responsibilities, written procedures, and adequate resources to ensure
that each PET drug is produced in accordance with the requirements.

\(x\) *Specification* means the quality standard (i.e., tests,
analytical procedures, and acceptance criteria) used to confirm the
quality of drug substances, drug products, intermediates, raw materials,
reagents, and other components including container closure systems, and
in-process controls.

\(y\) *Strength* means the concentration of the drug substance (for
example, radioactivity amount/volume).

\(z\) *Theoretical yield* means the quantity that would be produced at
any appropriate phase of production of a particular drug product, based
on the quantity of components to be used, in the absence of any loss or
error in production.

(aa) *Validation* means confirmation by examination and provision of
objective documented evidence that the particular requirements for a
specific intended use can be consistently fulfilled.

(bb) *Verification* means confirmation by examination and provision of
objective evidence that specified requirements have been fulfilled.

A:\\PETREG2899