Compliance Program Program: Chapter 56: Drug Quality Assurance

FOOD AND DRUG ADMINISTRATION
COMPLIANCE PROGRAM PROGRAM 7356.002
CHAPTER 56: DRUG QUALITY ASSURANCE
SUBJECT: DRUG MANUFACTURING INSPECTIONS IMPLEMENTATION DATE

Revision Note: Program revised to add potential OAI reporting responsibilities 10/31/2017
and to align with the CDER and ORA agreement, Concept of Operations for COMPLETION DATE
Facility Evaluation and Inspection.
DATA REPORTING
PRODUCT CODES PRODUCT/ASSIGNMENT CODES
All Human Drugs Domestic/Foreign surveillance inspections covered under this program, 7356.002, include
inspection of any facility that does not have a specific program:
PAC Type Subject
Industry codes: 56002 Full Drug Process Inspections (DPI)

56002H Abbreviated Drug Process Inspections (DPI)
50, 54-56, 59, 60-66
Report coverage of the surveillance programs specified below under the following PACs:
PAC Type Subject

56002A Full DPI/Small Volume Parenterals (CPGM: Sterile Drug
Process Inspections)
56002I Abbreviated DPI/Small Volume Parenterals (CPGM: Sterile Drug
Process Inspections)
56002B Full DPI/Drug Repackers and Relabelers
56002J Abbreviated DPI/Drug Repackers and Relabelers
56002C Full DPI/Radioactive Drugs
56002K Abbreviated DPI/Radioactive Drugs
56002F Full Active Pharmaceutical Ingredient Process Inspections
56002L Abbreviated Active Pharmaceutical Ingredient Process Inspections
56002P Full Drug Process Inspections - PET Domestic (CPGM:
PET CGMP Drug Process and Pre- Approval
Inspections/Investigations)
56002Q Abbreviated Drug Process Inspections - PET Domestic (CPGM:
PET CGMP Drug Process and Pre- Approval
Inspections/Investigations)
Note: The following three surveillance programs are reported under single PACs; there are no
full or abbreviated specific PACs:
PAC Subject
56002E DPI/Medical Gas Manufacturers (CPGM: Compressed Medical Gases)
56002M DPI/Therapeutic Biological Product Inspections (CPGM: Inspections of
Licensed Biological Therapeutic Drug Products)
56002S Drug Process Inspections - Biosimilars
56843 Post Approval Inspections/Investigations
(Continued on next page)
Date of Issuance: 10/31/2017 Page 1 of 29

FIELD REPORTING REQUIREMENTS
The ORA division completes the Establishment Inspection Report (EIR), including an inspection
classification consistent with Field Management Directive (FMD) 86 and FDA policies governing
pharmaceutical quality including this compliance program, within ORA established timeframes.
The ORA division files the inspection documents electronically no later than 45 calendar days from
the close of the inspection using the specific module (eNSpect, or Compliance Management System
(CMS)) accessible to both Office of Regulatory Affairs (ORA) and CDER (Center for Drug
Evaluation and Research).
ORA divisions should, as soon as practical, report significant inspection issues into FACTS, as per
the Investigations Operations Manual (IOM). For inspections initially classified as Official Action
Indicated (OAI) due to failure to comply with Current Good Manufacturing Practice (CGMP),
submit the written classification analysis and electronic documents to CDER’s Office of Compliance
(OC), Office of Manufacturing Quality (OMQ) for evaluation via CMS.1
ORA divisions (e.g., Pre-Approval Program Managers (PAMs)) are responsible for timely reporting
of potential OAI (pOAI) alerts into Panorama2 as per the current procedures.3 The PAM should take
into consideration the following when entering a pOAI alert into Panorama:
1. For surveillance coverage that may result in an OAI status, enter a pOAI alert into Panorama,
as soon as practical, but at most within 2 days of closing the inspection.
2. Enter a pOAI alert for the refusal of an inspection.4
3. If surveillance and pre-approval coverage are provided during the same inspection:
- Do not enter a pOAI alert for significant application-specific pre-approval issues
which do not impact marketed product; refer to CPGM 7346.832.
- Do enter a pOAI alert for significant surveillance issues (see point 1).
The PAM must remove the pOAI alert in Panorama as soon as practical if the ORA division decides
to change the initial recommendation of OAI. If CDER/OC/OMQ decides to change the initial OAI
recommendation, OMQ must update or remove the pOAI alert associated with that initial
classification in Panorama as soon as practical.
During an inspection, if you obtain information pertaining to inadequate adverse drug experience
(ADE) reporting, unapproved drug issues, or post-approval reporting violations (failing to submit
application supplements, Field Alert Reports (FARs), etc.), report in accordance with directions
1 For further information see Part V Regulatory/Administrative Strategy

2
PANORMA: CDER Time Reporting and Workflow Management System
3
Refer to Panorama Step-By-Step guides for creating, editing and closing pOAI alerts.
4 Guidance for Industry Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection.
See https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm360484.pdf

provided in the applicable compliance programs and under separate captions in the EIR. Data system
information about these inspectional activities should be reported under separate Program
Assignment Codes (PACs). Expansion of coverage under these programs into a CGMP inspection
should be reported under this compliance program.
The ORA divisions should use this revised compliance program for all CGMP inspections satisfying
the statutory obligation for periodic risk-based inspections of drug production. The instructions
provided in this section and elsewhere in this program governing ORA and CDER interactions
supersede the instructions in the other programs for the 5600 PACs (e.g., 7356.002A, 7356.002F,
7356.002P), with the exception of inspections reported under PAC 56843.
Note that Active Pharmaceutical Ingredient (API) and Positron Emission Tomography (PET) drug
inspections are performed to verify conformance with different quality standards and have their own
compliance programs. API inspections per CPGM 7356.002F are conducted to verify adherence to
section 501(a)(2)(B) of the Food, Drug, and Cosmetic Act using ICH Q7 as a guideline. PET
inspections per CPGM 7356.002P are conducted to verify adherence to 21 CFR Part 212.

PART I - BACKGROUND
Until 2012, FDA was required to inspect domestic establishments that manufacture drugs marketed
in the United States every 2 years, but there was no comparable requirement for inspecting foreign
establishments. The Food and Drug Administration Safety and Innovation Act (FDASIA),5 which
amended the FD&C Act section 510(h), eliminated this distinction, directing FDA to take a risk-
based approach to inspecting both domestic and foreign drug manufacturing establishments. The
selection of both domestic and foreign establishments for routine surveillance inspections is now
driven by a risk-based site selection model. In 2015 the agency formalized its process for selecting
establishments for inspection based on risk factors specified by section 510(h) of the Act.
This compliance program provides surveillance inspection coverage of drug manufacturing
establishments complying with the requirements of CGMP as per 501(a)(2)(B) of the Act and
implementing regulations. The focus of surveillance inspections is on system-wide controls that
ensure manufacturing processes produce quality drugs. Systems examined during these inspections
include those related to materials, quality control, production, facilities and equipment, packaging
and labeling, and laboratory controls.
FDA expects that establishments that comply with CGMP are likely to operate in a state of control
and consistently manufacture drug products of acceptable quality. FDA will use information
gathered from surveillance inspections to, among other things, make assessments about
manufacturing facilities listed in pending drug applications.
The inspectional guidance in this program is structured to provide for efficient use of resources
devoted to routine surveillance coverage, recognizing that in-depth coverage of all systems and all
processes is not feasible or required for all firms and inspections. It also provides guidance for
conducting for-cause inspections as appropriate (see page 9 under PROGRAM MANAGEMENT
INSTRUCTIONS).
5 Food and Drug Administration Safety and Innovation Act (FDASIA),

see https://www.gpo.gov/fdsys/pkg/PLAW-112publ144/pdf/PLAW-112publ144.pdf, page 1067.

PART II- IMPLEMENTATION
OBJECTIVES
The goal of this program's activities is to ensure that establishments consistently manufacture drug
products of acceptable quality and minimize consumers' exposure to adulterated drug products.
Under this program, inspections, investigations, sample collections, sample analyses, and regulatory
or administrative follow-up are made in order to identify quality problems and adverse trends at
establishments, so that FDA can develop strategies to mitigate them. The objectives of this program
are:
• to determine whether inspected firms are operating in compliance with applicable CGMP
requirements, and if not, to provide the evidence for actions to prevent adulterated products
from entering the market; as appropriate, to remove adulterated products from the market,
and to take action against persons responsible;
• to provide an assessment of firms’ conformance to CGMP requirements for Agency

decisions;
• to provide input to firms during inspections to improve their compliance with regulations;
and,
• to better understand current practices in drug manufacturing for the purpose of updating the
CGMP requirements, regulatory policy, and guidance documents.
STRATEGY
A. Inspection of Manufacturing Establishments (includes repackaging, contract labs, etc.)
Drug products are manufactured using many physical operations that bring together components,
and containers and closures to make a product that is released for distribution. Drug manufacturing
can be organized into sets of operations and related activities, called systems. Control of all systems
helps to ensure the firm will produce drugs that are safe, have the identity and strength, and meet the
quality and purity characteristics as intended.
This program applies to all manufacturing operations at the establishment.
It is not practical for FDA to audit every aspect of CGMP in every manufacturing facility during
every inspection visit. Profile classes generalize inspection coverage from a small number of
specific products to all the products in that class. Reporting coverage for every profile class as
defined in FACTS, for each inspection, provides the most broadly resource-efficient approach. This
program uses a risk-based systems approach to further generalize inspection coverage from a small
number of profile classes to an overall evaluation of the firm. Risk-based inspectional approaches
allow updating of all profile classes.

The inspection is defined as audit coverage of two or more systems, with mandatory coverage of the
Quality System (see system definitions below). Depending on the purpose of the inspection,
inspection coverage may include different numbers of systems. Inspecting the minimum number of
systems, or more systems as deemed necessary by the ORA division, will provide the basis for an
overall CGMP classification decision.
B. Inspection of Systems
Inspections of drug manufacturers should be made and reported using the system definitions and
industry codes in this compliance program. Focusing on systems, rather than profile classes, will
increase efficiency in conducting inspections because the systems are often applicable to multiple
profile classes. System inspection coverage should represent all profile classes at the establishment
and determine their acceptability/non-acceptability.
Coverage of a system should be sufficiently detailed, with specific examples selected, so that the
system inspection outcome reflects the state of control in that system for every profile class. If a
particular system is adequate, it should be adequate for all profile classes manufactured by the firm.
For example, the way a firm handles "materials" (i.e., receipt, sampling, testing, acceptance, etc.),
should be the same for all profile classes. An inspection does not have to include each profile class
attribute when covering a given system provided that inspection coverage includes related controls
for all types of drugs and operations. Likewise in the Production System, there are general
requirements like SOP use, charge-in of components, equipment identification, in- process sampling
and testing which can be evaluated through selection of example products in various profile classes.
Under each system there may be something unique for a particular profile class: e.g., under the
Materials System, the production of Water for Injection USP for use in manufacturing. Selecting
unique functions within a system will be at the discretion of the lead investigator. Any given
inspection need not cover every system. See Part III.
Complete inspection of one system may necessitate further follow up of some items within the
activities of another/other system(s) to fully document the findings. However, this coverage does not
constitute nor require complete coverage of these other systems.
C. A Scheme of Systems for the Manufacture of Drugs/Drug Products

The overall theme in devising the following scheme of systems was the subchapter structure of the 21
CFR 211 CGMP regulations. Every effort was made to group whole subchapters together in a rational
set of six systems which incorporates the general scheme of pharmaceutical manufacturing
operations.
The organization and personnel, including appropriate qualifications and training, employed in any
given system, will be evaluated as part of that system's operation. Production, control, and
distribution records required to be maintained by the CGMP regulations and selected for review
should be included for inspection audit within the context of each of the above systems. Inspections
of contract companies should be within the system for which the product or service is contracted as
well as their Quality System.

A general scheme of systems for auditing the manufacture of drugs and drug products consists of the
following:
1) Quality System. This system assures overall compliance with CGMPs and internal procedures
and specifications. This system includes the quality control unit and all of its review and
approval duties (e.g., change control, reprocessing, batch release, annual record review,
validation protocols, and reports, etc.). It includes all product defect evaluations and
evaluation of returned and salvaged drug products. See the CGMP regulations, 21 CFR 211
Subparts B, E, F, G, I, J, and K.
2) Facilities and Equipment System. This system includes the measures and activities which
provide an appropriate physical environment and resources used in the production of the drugs
or drug products. It includes:
a) Buildings and facilities along with maintenance;
b) Equipment qualifications (installation and operation); equipment calibration and
preventative maintenance; and cleaning and validation of cleaning processes as
appropriate. Process performance qualification will be evaluated as part of the
inspection of the overall process validation which is done within the system where the
process is employed; and,
c) Utilities that are not intended to be incorporated into the product such a HVAC,
compressed gases, steam and water systems.
See the CGMP regulations, 21 CFR 211 Subparts B, C, D, and J.
3) Materials System. This system includes measures and activities to control finished products,
components, including water or gases that are incorporated into the product, containers and
closures. It includes validation of computerized inventory control processes, drug storage,
distribution controls, and records. See the CGMP regulations, 21 CFR 211 Subparts B, E, H,
and J.
4) Production System. This system includes measures and activities to control the manufacture
of drugs and drug products including batch compounding, dosage form production, in-process
sampling and testing, and process validation. It also includes establishing, following, and
documenting performance of approved manufacturing procedures. See the CGMP regulations,
21 CFR 211 Subparts B, F, and J.
5) Packaging and Labeling System. This system includes measures and activities that control
the packaging and labeling of drugs and drug products. It includes written procedures, label
examination and usage, label storage and issuance, packaging and labeling operations
controls, and validation of these operations. See the CGMP regulations, 21 CFR 211 Subparts
B, G, and J.
6) Laboratory Control System. This system includes measures and activities related to
laboratory procedures, testing, analytical methods development and validation or verification,
and the stability program. See the CGMP regulations, 21 CFR 211 Subparts B, I, J, and K.

As this program approach is implemented, the experience gained will be reviewed to make
modifications to the system definitions and organization as needed.
PROGRAM MANAGEMENT INSTRUCTIONS
A. Definitions
1. Surveillance Inspections
The Full Inspection Option

The Full Inspection Option is a surveillance inspection meant to provide a broad and in-depth
evaluation of the firm's conformance with CGMP requirements. A Full Inspection may change to an
Abbreviated Inspection Option with concurrence of the ORA division. During the course of a Full
Inspection, verification of Quality System activities may require limited coverage in other systems. The
Full Inspection Option will normally include an inspection audit of at least four of the systems, one of
which must be the Quality System (the system which includes the responsibility for the annual product
reviews).
The Abbreviated Inspection Option

The Abbreviated Inspection Option is a surveillance inspection meant to provide an efficient updated
evaluation of a firm's conformance with CGMP requirements. The abbreviated inspection will
provide documentation for continuing a firm in a satisfactory CGMP compliance status. Generally
this will be done when a firm has a record of satisfactory CGMP compliance, with no significant
recall, or product defect or alert incidents, or with little shift in the manufacturing profiles of the firm
since the last inspection. See Part III, Section B.2. An Abbreviated Inspection may change to a Full
Inspection, upon findings of objectionable conditions (as listed in Part V) in one or more systems,
with ORA division concurrence. The Abbreviated Inspection Option normally will include an
inspection audit of at least two of the systems, one of which must be the Quality System (the system
which includes the responsibility for the annual product reviews). The ORA division drug program
managers should ensure that the optional systems are rotated in successive Abbreviated Inspections.
During the course of an abbreviated inspection, verification of quality system activities may require
limited coverage in other systems. Some firms participate in a limited part of the production of a drug
or drug product, e.g., a contract laboratory. Such firms may employ only two of the systems defined.
In these cases the inspection of the two systems will comprise inspection of the entire firm and will
be considered the Full Inspection Option.
Selecting Systems for Coverage

The selection of the system(s) for coverage will be made by the ORA division based on the firm's
specific operation, history of previous coverage, history of compliance, or other priorities determined
by the ORA division.

2. For-Cause Inspections
A for-cause inspection is defined to include: (i) Follow-up compliance inspections performed to
verify corrective actions after a regulatory action has been taken; (ii) inspections performed in
response to specific events or information (Field Alert Reports (FARs), Biological Product Defect
Reports (BPDRs), industry complaints, recalls, and other indicators of defective products, etc.) that
bring into question the compliance and/or quality of a manufacturing practice, facility, process, or
drug.
For-cause inspections that are to be initiated and reported under this program include follow-up
compliance inspections performed to verify corrective actions after a regulatory action has been
taken. Follow-up compliance inspections provide focused coverage and include the areas of concern,
the proposed corrective action plan for impacted operations, any implemented corrective actions,
and/or the deficiencies noted on the FDA-483 for a previous inspection. The decision to add systems
coverage is made on case-by-case basis.
For-cause inspections in response to FARs defect reports are to be initiated and performed under
CPGM 7356.021.
Other for-cause inspections (e.g., industry complaints, other indicators of defective products) may be
initiated as per FMD-17, but expanded to include CGMP coverage for the purpose of updating overall
compliance status.
3. State of Control
A drug firm is considered to be operating in a state of control when it employs conditions and
practices that assure compliance with the intent of Sections 501(a)(2)(B) of the Act and the portions
of the CGMP regulations that pertain to their systems. A firm in a state of control produces finished
drug products for which there is an adequate level of assurance of quality, strength, identity and
purity.
A firm is out of control if any one system is out of control. A system is out of control if the quality,
identity, strength and purity of the products resulting from one or more system(s) cannot be
adequately assured. Documented CGMP deficiencies provide the evidence for concluding that a
system is not operating in a state of control. See Part V. Regulatory/Administrative Strategy for a
discussion of compliance actions based on inspection findings demonstrating out of control
systems/firm.
4. Drug Process
A drug process is a related series of operations which result in the preparation of a drug or drug
product. Major operations or steps in a drug process may include mixing, granulation, encapsulation,
tableting, chemical synthesis, fermentation, aseptic filling, sterilization, packing, labeling, testing, etc.
5. Drug Manufacturing Inspection

A drug manufacturing inspection is an establishment inspection in which two or more systems,
including the Quality System, are evaluated to determine if manufacturing is occurring in a state of
control.

B. Inspection Planning
ORA will conduct drug manufacturing inspections using a risk-based approach and maintain profiles
or other monitoring systems. The ORA division is responsible for determining the depth of coverage
given to each drug firm. The depth of inspection coverage should be determined by the firm's
compliance history, the manufacturing technology employed, and the characteristics of the products.
CGMP inspectional coverage shall be sufficient to assess the state of control and compliance for each
firm.
In advance of a scheduled Surveillance Inspection, the Office of Quality Surveillance (OQS) in the
Office of Pharmaceutical Quality (OPQ)/CDER prepares an up-to-date site dossier which includes
but is not limited to, quality information on facility inspection history, recalls, shortages, customer
complaints, foreign regulator inspection outcomes, information on submitted Field Alert Reports
(FARs) or Biological Product Defect Reports (BPDRs), submitted quality metrics data if available,
and a listing of all products manufactured at the site. When a system is inspected, the inspection of
that system may be considered applicable to all products which use it. Investigators should select an
adequate number and type of products to accomplish coverage of the system. Selection of products
should be made so that coverage is representative of the firm's overall abilities in manufacturing
within CGMP requirements.
Products posing special challenges, such as low dose products, narrow therapeutic range drugs,
combination products,6 modified release products, biological products, and new products
manufactured under recently approved drug applications, should be considered first in selecting
products for coverage (refer to IOM section 5.5.1.2 – Inspectional Approach7).
The health significance of certain CGMP deviations may be lower when the drug product involved
has no major systemic health effect or no dosage limitations such as in products like calamine lotion.
Such products should be given inspection coverage with appropriate priority.
Inspections for this compliance program may be performed during visits to a firm when operations
are being performed for other compliance programs or other investigations.
C. Profiles
The inspection findings will be used as the basis for updating all profile classes in the profile screen
of the FACTS EIR coversheet that is used to record profile/class determinations. Normally, an
inspection under this risk-based systems approach will result in all profile classes being updated.
6
Combination products are subject to the CGMP requirements outlined in 21 CFR Part 4. See the FDA Guidance for
Industry and Staff: Current Good Manufacturing Practice Requirements for Combination Products for more
information at https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM429304.pdf.
7
Investigations Operations Manual, https://www.fda.gov/downloads/ICECI/Inspections/IOM/UCM150576.pdf

PART III – INSPECTIONAL
INVESTIGATIONAL OPERATIONS
A. General
Review and use the CGMP regulations for Finished Pharmaceuticals (21 CFR 210 and 211) and
related guidance for industry to evaluate manufacturing processes.
The investigator should conduct inspections according to the STRATEGY section in Part II of this
compliance program. Recognizing that drug firms vary greatly in size and scope, and manufacturing
systems are more or less sophisticated, the approach to inspecting each firm should be carefully
planned. For example, it may be more appropriate to review the Quality System thoroughly before
entering production areas in some firms; in others, the Quality System review should take place
concurrently with inspection of another system or systems selected for coverage. The complexity and
variability necessitate a flexible inspection approach; one which allows the investigator to choose the
inspection focus and depth appropriate for a specific firm, but also one which directs the performance
and reporting on the inspection within a framework which will provide for a uniform level of CGMP
assessment. Furthermore, this inspection approach will provide for fast communication and
evaluation of findings.
Inspectional observations noting CGMP deficiencies should be related to a requirement. CGMP

requirements for manufacture of drug products (dosage forms) are in section 501(a)(2)(B) of the
FD&C Act and the regulations, and are amplified by guidance, case precedents, etc. CGMP
requirements apply to the manufacture of all human drugs, which include prescription and non-
prescription drug products, drug products that are the subject of pending applications, drug products
used in clinical trials, as well as products not requiring approval.
Active Pharmaceutical Ingredient (API) and Positron Emission Tomography (PET) drug inspections
are performed to verify conformance with different quality standards than 21 CFR 210 and 211 and
have their own compliance programs. API inspections are conducted under CPGM 7356.002F, which
employs ICH Q7 as a quality standard, and establishes compliance to the statutory requirement of the
section 501(a)(2)(B) of the FD&C Act. Firms that follow ICH Q7 generally will be considered to
comply with the statutory requirement. PET inspections under CPGM 7356.002P are conducted to
verify adherence to 21 CFR Part 212.
Guidance documents are not to be referred to as the justification for an inspectional observation. The
justification comes from the statute and the CGMP regulations. Current Guides to Inspection and
Guidance to Industry documents provide interpretations of requirements, which may assist in the
evaluation of the adequacy of CGMP systems. Guidance documents do not establish requirements.
Current inspectional observation policy as stated in the IOM says that the FDA-483, when issued,
should be specific and contain only significant items. For this program, inspection observations
should be organized under separate captions by the systems defined in this program. List the
observations in order of importance within each system. Where repeated or similar observations are
made, they should be consolidated under a unified observation. A limited number of observations can

be common to more than one system (e.g., organization and personnel including appropriate
qualifications and training). In these instances, put the observation in the first system reported on the
FDA-483 and in the text of the EIR, reference the applicability to other systems where appropriate.
This is being done to accommodate the structure of eNSpect which allows individual citation once
per FDA-483. Refrain from using unsubstantiated conclusions. Do not use the term "inadequate"
without explaining why and how. Refer to policy in the IOM, Chapter 5, Section 5.2.3 – Reports of
Observations for further guidance on the content of Inspectional Observations.
Specific specialized inspectional guidance may be provided as attachments to this program, or in

requests for inspection, assignments, etc.
B. Inspection Approaches
This program provides two surveillance inspectional options, Full Inspection Option and the
Abbreviated Inspection Option . See the definitions of the inspection options in Part II of this
program.
1. Selecting the Full Inspection Option. The Full Inspection Option will include inspection of
at least four of the systems listed in Part II Strategy, one of which must be the Quality System.
a) Select the Full Inspection Option for an initial FDA inspection of newly registered
establishments. Inspection coverage should include all systems as appropriate to the
operations. A Full Inspection may change to the Abbreviated Inspection Option, with
ORA division concurrence.
For efficient use of FDA resources, before scheduling the surveillance coverage of the
newly registered establishment, the ORA division should consult with CDER to
determine whether it is listed in any pending application and also needs a pre-approval
inspection.
b) Select the Full Inspection Option when the firm has a history of fluctuating into and out
of compliance. To determine if the firm meets this criterion, the ORA division should
utilize all information at its disposal, such as inspection results, results of sample
analyses, complaints, DQRS and BPDR reports, recalls, etc. and the compliance actions
resulting from them or from past inspections.
c) Evaluate if important changes have occurred by comparing current operations against the
EIR for the previous Full Inspection. The following types of changes are typical of those
that warrant the Full Inspection Option:
1) New potential for cross-contamination arising through change in process or product
line.
2) Use of new technology requiring new expertise, significant new equipment, or new
facilities.
d) A Full Inspection may also be conducted on a surveillance basis at the ORA division’s
discretion.

2. Selecting the Abbreviated Inspection Option. The Abbreviated Inspection Option normally
will include inspection audit of at least two systems, one of which must be the Quality
System. During the course of an Abbreviated Inspection, verification of quality system
activities may require limited coverage in other systems
a) This option involves an inspection of the manufacturer to maintain surveillance over the
firm's activities and to provide input to the firm on maintaining and improving the
CGMP level of assurance of quality of its products.
b) A Full Inspection may change to the Abbreviated Inspection option, with ORA division
concurrence, based on inspection history.
c) Abbreviated Inspection coverage may be changed to the Full Inspection Option at the
discretion of the ORA division.
Inspection Coverage
It is not anticipated that Full Inspections (4 to 6 systems coverage) can be conducted every time. To
build comprehensive information on the firm's manufacturing activities, ORA divisions should
consider selecting different systems for inspection coverage during successive Abbreviated
Inspections.
Follow up inspections to a Warning Letter or other significant regulatory actions are considered for-
cause inspections, and as a result, the related for-cause assignments can request either full systems
coverage or individual system coverage. In addition, coverage can be added on case-by-case basis at
the discretion of the ORA division prior to or during the inspection.
C. System Inspection Coverage
QUALITY SYSTEM
Assessment of the Quality System is two-phased. The first phase is to evaluate whether the Quality
Control Unit has fulfilled the responsibility to review and approve all procedures related to
production, quality control, and quality assurance and assure the procedures are adequate for their
intended use. This also includes the associated recordkeeping systems. The second phase is to assess
the data collected to identify quality problems which may link to other major systems for inspectional
coverage.
For each of the following, the firm should have written and approved procedures and documentation
resulting therefrom. The firm's adherence to written procedures should be verified through
observation whenever possible. These areas are not limited to finished products, but may also
incorporate components and in-process materials. These areas may indicate deficiencies not only in
this system but also in other major systems that would warrant expansion of coverage.
All areas under this system should be covered; however, the depth of coverage may vary depending
upon inspectional findings.

- Product reviews: at least annually; should include information from areas listed below as
appropriate; batches reviewed, for each product, are representative of all batches
manufactured; trends are identified; refer to 21 CFR 211.180(e)
- Complaint reviews (quality and medical): documented; evaluated; investigated in a timely

manner; includes corrective action where appropriate
- Discrepancy and failure investigations related to manufacturing and testing: documented;

evaluated; investigated in a timely manner; includes corrective action where appropriate
- Change Control: documented; evaluated; approved; need for revalidation assessed
- Product Improvement Projects: for marketed products
- Reprocess/Rework: evaluation, review and approval; impact on validation and stability
- Returns/Salvages: assessment; investigation expanded where warranted; disposition
- Rejects: investigation expanded where warranted; corrective action where appropriate
- Stability Failures: investigation expanded where warranted; need for field alerts evaluated;
disposition
- Quarantine products
- Validation: status of required validation/revalidation (e.g., computer, manufacturing

process, laboratory methods)
- Training/qualification of employees in quality control unit functions
FACILITIES AND EQUIPMENT SYSTEM
observation whenever possible. These areas may indicate deficiencies not only in this system but also
in other systems that would warrant expansion of coverage. When this system is selected for coverage
in addition to the Quality System, all areas listed below should be covered; however, the depth of
coverage may vary depending upon inspectional findings.
1. Facilities
- cleaning and maintenance
- facility layout and air handling systems for prevention of cross-contamination (e.g.,
penicillin, beta-lactams, steroids, hormones, cytotoxics)

- specifically designed areas for the manufacturing operations performed by the firm to
prevent cross-contamination or mix-ups
- general air handling systems
- control system for implementing changes in the building
- lighting, potable water, washing and toilet facilities, sewage and refuse disposal
- sanitation of the building, use of rodenticides, fungicides, insecticides, cleaning and

sanitizing agents
2. Equipment
- equipment installation and operational qualification where appropriate
- adequacy of equipment design, size, and location
- equipment surfaces should not be reactive, additive, or absorptive
- appropriate use of equipment operations substances, (lubricants, coolants, refrigerants,

etc.) contacting products/containers
- cleaning procedures and cleaning validation for re-usable or multi-product equipment
- controls to prevent contamination, particularly with any pesticides or any other toxic
materials, or other drug or non-drug chemicals
- qualification, calibration and maintenance of storage equipment, such as refrigerators

and freezers for ensuring that standards, raw materials, reagents, etc. are stored at the
proper temperatures
- equipment qualification, calibration and maintenance, including computer

qualification/validation and security
- control system for implementing changes in the equipment
- equipment identification practices (where appropriate)
- documented investigation into any unexpected discrepancy
MATERIALS SYSTEM

this system but also in other systems that would warrant expansion of coverage. When this system is
selected for coverage in addition to the Quality System, all areas listed below should be covered;
however, the depth of coverage may vary depending upon inspectional findings.
- training/qualification of personnel
- identification of components, containers, closures
- inventory of components, containers, closures
- storage conditions
- storage under quarantine until tested or examined and released
- representative samples collected, tested or examined using appropriate means
- at least one specific identity test is conducted on each lot of each component
- a visual identification is conducted on each lot of containers and closures
- testing or validation of supplier's test results for components, containers and closures
- rejection of any component, container, closure not meeting acceptance requirements

- Investigate fully the firm's procedures for verification of the source of components.
- appropriate retesting/reexamination of components, containers, closures
- first in – first out use of components, containers, closures
- quarantine of rejected materials
- water and process gas supply, design, maintenance, validation and operation
- containers and closures should not be additive, reactive, or absorptive to the drug product
- control system for implementing changes in the materials handling operations
- qualification/validation and security of computerized or automated processes
- finished product distribution records by lot

PRODUCTION SYSTEM
- control system for implementing changes in processes
- adequate procedure and practice for charge-in of components
- formulation/manufacturing at not less than 100%
- identification of equipment with contents, and where appropriate phase of manufacturing

and/or status
- validation and verification of cleaning/sterilization/ depyrogenation of containers and

closures
- calculation and documentation of actual yields and percentage of theoretical yields
- contemporaneous and complete batch production documentation
- established time limits for completion of phases of production
- implementation and documentation of in-process controls, tests, and examinations (e.g.,

pH, adequacy of mix, weight variation, clarity)
- justification and consistency of in-process specifications and drug product final

specifications
- prevention of objectionable microorganisms in non-sterile drug products
- adherence to preprocessing procedures (e.g., set-up, line clearance)
- equipment cleaning and use logs
- master production and control records
- batch production and control records

- process validation, including validation and security of computerized or automated

processes
- change control; the need for revalidation evaluated
PACKAGING AND LABELING SYSTEM
observation whenever possible. These areas are not limited only to finished products, but also
- acceptance operations for packaging and labeling materials
- control system for implementing changes in packaging and labeling operations
- adequate storage for labels and labeling, both approved and returned after issued
- control of labels which are similar in size, shape, and color for different products
- finished product cut labels for immediate containers which are similar in appearance
without some type of 100 percent electronic or visual verification system or the use of
dedicated lines
- gang printing of labels is not done, unless they are differentiated by size, shape, or color
- control of filled unlabeled containers that are later labeled under multiple private labels
- adequate packaging records that will include specimens of all labels used
- control of issuance of labeling, examination of issued labels and reconciliation of used

labels
- examination of the labeled finished product
- adequate inspection (proofing) of incoming labeling
- use of lot numbers, destruction of excess labeling bearing lot/control numbers

- physical/spatial separation between different labeling and packaging lines
- monitoring of printing devices associated with manufacturing lines
- line clearance, inspection and documentation
- adequate expiration dates on the label
- conformance to tamper-resistant packaging requirements (see 21CFR 211.132 and

Compliance Policy Guide, Sec. 450.500)8
- validation of packaging and labeling operations including validation and security of

computerized processes
LABORATORY CONTROL SYSTEM
observation whenever possible. These areas are not limited only to finished products, but may also
incorporate components and in-process materials. These areas may indicate
deficiencies not only in this system but also in other systems that would warrant expansion of
coverage. When this system is selected for coverage in addition to the Quality System, all areas listed
below should be covered; however, the depth of coverage may vary depending upon inspectional
findings.
- adequacy of staffing for laboratory operations
- adequacy of equipment and facility for intended use
- calibration and maintenance programs for analytical instruments and equipment
- validation and security of computerized or automated processes
- reference standards; source, purity and assay, and tests to establish equivalency to current
official reference standards as appropriate
- system suitability checks on chromatographic systems (e.g., GC or HPLC)
8 CPG Sec. 450.500 Tamper-Resistant Packaging Requirements for Certain Over-the-Counter Human Drug Products.
See https://www.fda.gov/iceci/compliancemanuals/compliancepolicyguidancemanual/ucm074391.htm

- specifications, standards, and representative sampling plans
- adherence to the written methods of analysis
- validation/verification of analytical methods
- control system for implementing changes in laboratory operations
- required testing is performed on the correct samples
- complete analytical records from all tests and summaries of results
- quality and retention of raw data (e.g., chromatograms and spectra)
- correlation of result summaries to raw data; presence of unused data
- adherence to an adequate Out of Specification (OOS) procedure which includes timely

completion of the investigation
- adequate reserve samples; documentation of reserve sample examination
- stability testing program, including demonstration of stability indicating capability of the

test methods
D. Sampling
Samples of defective product constitute persuasive evidence that significant CGMP problems exist.
Physical samples may be an integral part of a CGMP inspection where control deficiencies are
observed. Physical samples should be correlated with observed control deficiencies. Contact program
coordinator (chemistry, microbiology) in ORS/OMPTSLO identified in CONTACTS for guidance
and types of samples (in process or finished product) to be collected and for appropriate servicing
laboratory. Documentary samples may be submitted when the documentation illustrates the
deficiencies better than a physical sample. ORA divisions may elect to collect, but not analyze,
physical samples, or to collect documentary samples to document CGMP deficiencies. Physical
sample analysis is not necessary to document CGMP deficiencies.
When a large number of products have been produced under deficient controls, collect physical
and/or documentary samples of products which have the greatest therapeutic significance, narrow
therapeutic range, or low dosage strength. Include samples of products of minimal therapeutic
significance only when they illustrate highly significant CGMP deficiencies.
For sampling guidance, refer to IOM, Chapter 4 – Sampling.

E. Inspection Teams
An inspection team (see IOM section 5.1.2.5 – Team Inspections) composed of experts from within
the Division, other ORA divisions, or Headquarters is encouraged when it provides needed expertise
and experience. Contact ORA/Office of Pharmaceutical Quality Operations if technical assistance is
needed (see also FMD 142). ORA leads the inspection with CDER participation, when requested by
ORA. Participation of an analyst (chemist or microbiologist) on an inspection team is also
encouraged, especially where laboratory issues are extensive or complex. Contact your Drug
Servicing Laboratory or ORA/Office of Regulatory Science. Each inspection team member is
responsible for preparing for, executing, and documenting the inspection, including contributing to
the establishment inspection report, which documents the items covered during the inspection, within
established timeframes.
F. Reporting
If ORA observes critical conditions (e.g., which may result in an imminent health hazard), as
appropriate and if feasible, they may be discussed between ORA and OMQ before the inspection
closes. The ORA Director of Investigations Branch or designee, the investigator(s), and OMQ
collaboratively decide whether to continue the inspection to gather additional information or to close
the inspection to initiate prompt regulatory action.
The investigator will utilize IOM Subchapter 5.10 – Reporting for guidance in reporting of
inspectional findings. Identify systems covered in the Summary of Findings. Identify and explain in
the body of the report the rationale for inspecting the profile classes covered. Report and discuss in
full any adverse findings by systems under separate captions. Add additional information as needed
or desired, for example, a description of any significant changes that have occurred since previous
inspections. Each report should include a description of operations, products, and controls covered
during the inspection in sufficient detail to enable appropriate regulatory decision-making following
the inspection and to inform future inspections.
FDA’s pharmaceutical CGMP inspection program and resulting inspection reports are of interest to
counterpart inspectorates and regulators worldwide who use and rely on FDA inspections and
inspection reports, as does FDA of their inspections and reports.
Reports with specific, specialized information required should be prepared as instructed within the
individual assignment/attachment.

PART IV - ANALYTICAL
ANALYZING LABORATORIES
The types of analyses that may be performed under this program include (but are not limited to);
• Routine analyses: Assay, Impurities, Dissolution, Identification
• Routine microbiological analyses: Sterility, Endotoxin, Nonsterile examination
• Other microbiological examinations
• Chemical Cross Contamination
• Antibiotics
• Bioassays
• Particulate Matter in Injectables
SERVICING LABORATORY
Contact (email) ORAHQ ORS Management <[email protected]> for
servicing laboratory(s) for all chemical and microbiological testing. When contacting ORS for
servicing laboratories provide product description, lots to be tested, analyses to be performed, and
reason for the sample collection. Servicing laboratories will be identified based on lab specialization,
technology and testing expertise, and laboratory capacity.
[NOTE: The Laboratory Servicing Table (LST) Dashboard is not sufficiently detailed to accurately,
correctly identify laboratories and should not be used for selecting servicing laboratories under this
program.]
ANALYSIS:
1. Samples are to be examined for compliance with applicable specifications as they relate to
deficiencies noted during the inspection. All analyses will be performed by the official regulatory
methods, or when no official method exists, by other validated procedures identified by
ORS/OMPTSLO.
2. The presence of cross-contamination must be confirmed by a mass spectroscopic method.
3. Check Analysis for dissolution rate must be performed by a second dissolution-testing laboratory.
4. Microbiological examinations should be based on appropriate sections of USP and

Pharmaceutical Microbiological Manual (PMM).9
9 Pharmaceutical Microbiological Manual (PMM), ORA.007,

See https://www.fda.gov/downloads/scienceresearch/fieldscience/ucm397228.pdf

PART V - REGULATORY/ADMINISTRATIVE STRATEGY
Inspection findings that demonstrate that a firm is not operating in a state of control may be used as
evidence for taking appropriate advisory, administrative, and/or judicial actions.
The initial classification should be based on the ORA division’s assessment of the seriousness of the
CGMP problem.
The endorsement of the inspection report should point out the actions by the firm that have been
taken or will be taken and when. All deficiencies noted in inspections/audits under this program must
be addressed by stating the firm's corrective actions, accomplished or projected, for each as
established in the discussion with management at the close of the inspection.
All corrective actions proposed by firms are monitored and managed collaboratively by the ORA
division and OMQ. These approaches may range from shut down of operations, recall of products,
conducting testing programs, development of new procedures, modifications of plants and equipment,
to simple immediate corrections of conditions. CDER OPQ sub-offices (Office of Pharmaceutical
Manufacturing Assessment (OPMA) and/or OQS) will also assist ORA divisions as requested.
If an inspection report documents that one or more systems at the establishment is/are out of control,
the inspection should receive an initial OAI classification. Issuance of a Warning Letter or taking
other regulatory or advisory actions pursuant to a surveillance inspection should result in the
classification of all profile classes as unacceptable. Also, the inspection findings will be used as the
basis for updating profile classes in FACTS.
FDA laboratory tests that demonstrate effects of absent or inadequate current good manufacturing
practice are strong evidence for supporting regulatory actions. Such evidence development should be
considered as an inspection progresses and deficiencies are found. However, the lack of violative
physical samples is not a barrier to pursuing regulatory and/or administrative action provided that
CGMP deficiencies have been well documented. Likewise, physical samples found to be in
compliance are not a barrier to pursuing action under CGMP charges.
Evidence to support significant and/or a trend of deficiencies within a system covered could
demonstrate the failure of a system and should result an OAI referral to OMQ. When deciding the
type of action to recommend, the initial decision should be based on the seriousness and/or the
frequency of the problems. Examples of such problems include the following:
Quality System:
1) Pattern of failure to review/approve procedures
2) Pattern of failure to document execution of operations as required
3) Pattern of failure to review documentation
4) Pattern of failure to conduct investigations and resolve discrepancies/failures/

deviations/complaints

5) Pattern of failure to assess other systems to assure compliance with CGMP and SOPs
Facilities and Equipment
1) Contamination with filth, objectionable microorganisms, toxic chemicals or other drug

chemicals, or a reasonable potential for contamination, with demonstrated avenues of
contamination, such as airborne or through unclean equipment
2) Pattern of failure to validate cleaning procedures for non-dedicated equipment; Lack of

demonstration of effectiveness of cleaning for dedicated equipment
3) Pattern of failure to document investigation of discrepancies
4) Pattern of failure to establish/follow a control system for implementing changes in the

equipment
5) Pattern of failure to qualify equipment, including computers
Materials System
1) Release of materials for use or distribution that do not conform to established

specifications
2) Pattern of failure to conduct one specific identity test for components

materials handling operations
5) Lack of validation of water systems as required depending upon the intended use of the
water
6) Lack of validation of computerized processes
Production System

production system operations
3) Lack of process validation

5) Pattern of incomplete or missing batch production records
6) Pattern of nonconformance to established in-process controls, tests, and/or specifications
Packaging and Labeling

packaging and/or labeling operations
4) Lack of control of packaging and labeling operations that may introduce a potential for
mislabeling
5) Lack of packaging validation
Laboratory System

laboratory operations
3) Lack of validation of computerized and/or automated processes
4) Pattern of inadequate sampling practices
5) Lack of validated analytical methods
6) Pattern of failure to follow approved analytical procedures
7) Pattern of failure to follow an adequate OOS procedure
8) Pattern of failure to retain raw data
9) Lack of stability indicating methods
10) Pattern of failure to follow stability programs
Follow up to a Warning Letter or other significant regulatory action as a result of an abbreviated

inspection should warrant full inspection coverage as defined in this program.

PART VI – REFERENCES, ATTACHMENTS, AND PROGRAM CONTACTS
REFERENCES
• Federal Food, Drug, and Cosmetic Act, as amended

• Code of Federal Regulations, Title 21, Parts 4, 210 and 211, as revised
• Preamble to Code of Federal Regulations, Title 21, Parts 210 and 211 General Comments (1978)
• 21 CFR Part 11 Electronic Records: Electronic Signatures
• Inspection Operations Manual
• Regulatory Procedures Manual
• Compliance Policy Guides Manual, Chapter 4 Human Drugs
• Guidance for Industry10
 Pharmaceutical Quality/CMC11
 Pharmaceutical Quality/Manufacturing Standards (CGMP)12
 Pharmaceutical Quality/Microbiology13
 Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug
Inspection
 Current Good Manufacturing Practice Requirements for Combination Products
 ICH Guidelines14
- Q8(R2) Pharmaceutical Development
- Q9 Quality Risk Management
- Q10 Pharmaceutical Quality System
• Inspection Guides15
 Computerized Systems in Drug Establishments
 Guide to Inspections of Dosage Form Drug Manufacturers-CGMPs
 Guide to Inspections of Lyophilization of Parenterals
 Guide to Inspections of Pharmaceutical Quality Control Laboratories
 Guide to Inspections of High Purity Water Systems
 Guide to Inspections of Validation of Cleaning Processes
10 See https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
11
See https://www.fda.gov/drugs/pharmaceutical-quality-resources/guidances-and-manuals-pharmaceutical-quality
12 See https://www.fda.gov/drugs/pharmaceutical-quality-resources/guidances-and-manuals-pharmaceutical-quality
13 See https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064983.htm
14 See https://www.fda.gov/science-research/guidance-documents-including-information-sheets-and-notices/ich-guidance-documents
15 See https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-references/inspection-guides

ATTACHMENTS
Attachments to the Drug Process Inspection program may be issued for certain industries, dosage
forms, and processes with known problems or unique drug processes. These attachments will contain
the guidance needed to perform these specialized inspections.
Some of the attachments to be issued with this program may include reporting requirements
specifically designed to obtain industry-wide information on certain practices to permit evaluation of
the adequacy of FDA's regulatory efforts.
Attachments and/or reporting requirements will be periodically reviewed and evaluated and deleted
from the program when they are no longer needed.
CONTACTS
For technical questions concerning inspections contact: Office of Regulatory Affairs (ORA)
Office of Medical Products and Tobacco Operations (OMPTO)
Division of Medical Products and Tobacco Program Operations (DMPTPO) Telephone

number: 301-796-0358
Email: [email protected]
Office of Regulatory Science/

Office of Medical Products, Tobacco & Specialty Laboratory Operations (OMPTSLO)
Shari Kahn (Chemistry) 301-796-8154, [email protected]

Angele Smith (Microbiology) 301-796-4200, [email protected]
Center for Drug Evaluation and Research
CGMP or any Quality-Related Policy Questions

For CGMP or any quality-related policy question, technical or scientific questions or
information needs, including questions about this program, please send an email to the
following address and it will be handled as a top priority:
[email protected]
Enforcement-Related Guidance or Policy

For enforcement-related guidance or policy, including evidence need and sufficiency,
citations, and case evaluation/recommendation advice, please send an email
to the following address and it will be handled as a top priority:

CDER OMQ Compliance Policy

[email protected]
Labeling Requirements and Policies

Office of Unapproved Drugs and Labeling Compliance, see intranet home page for contacts
[CDER | Office of Compliance | Office of Unapproved Drugs and Labeling Compliance]
Registration and Drug Listing Requirements
CDER Office of Compliance, see “CDER: Who’s the Lead” intranet page for contacts
[CDER | Office of Communications | CDER: Who’s the Lead]

PART VII - CDER AND ORA RESPONSIBILITIES OVERVIEW
CDER and ORA recently redefined their roles and responsibilities with regard to application review and
inspections of human drugs facilities under the concept of operations (ConOps).16 This ConOps operating
model applies to pre- and post-approval, surveillance, and for-cause inspections. The roles and
responsibilities for surveillance and surveillance related for-cause inspections subject to this Program
7356.002 are summarized below.
Surveillance Inspection Responsibilities:

OQS uses a risk-based site selection model to identify facilities for inspection, and prepares an up-to-date
site dossier for each of the identified facilities in advance of a scheduled surveillance inspection. ORA
schedules surveillance inspections for individual sites. ORA leads surveillance facility inspections with
CDER participation, when requested by ORA. ORA then conducts an on-site inspection based on the
Surveillance Compliance Program and quality information summarized in the site dossier.
If the intial classification is OAI, the responsible ORA Division provides a written classification analysis,
including the electronic documents, to OMQ within 45 calendar days of closing the inspection. OMQ
makes a final classification with input from the Office of the Chief Counsel, if needed, and issues a
decisional letter in the following 45 calendar days (90 calendar days following the inspection closing). If an
inspection is classified as final OAI, OMQ, solely or in collaboration with ORA, takes an appropriate action
within 90 calendar days of the decisional letter. If OMQ determines that an advisory or enforcement action
is not warranted, ORA is notified of the change in classification. OMQ will then issue an FMD-
145/decisional letter no later than 90 calendar days following the inspection closing.
If the facility inspection results in an ORA recommendation for an NAI or VAI classification and no further
action is recommended, ORA issues an FMD-145/decisional letter within 90 calendar days following the
inspection closing.
For-Cause Inspection Responsibilities:

Requests for for-cause inspections can be initiated by ORA, OPMA, OQS, or OC. Once the initiating office
determines a for-cause inspection is warranted, the office prepares an assignment that sets forth the areas of
required coverage which may or may not include surveillance program coverage. If required, ORA
approves the assignment as per FMD-17, and schedules the inspection. ORA leads, and performs the
inspections with CDER participation, when appropriate.
ORA or CDER will not issue an FMD-145 letter without the concurrence of the initiating office. For-cause
inspections that result in surveillance program coverage and are initially classified OAI, will receive final
classification from OMQ in 90 days following the close of the inspection; OMQ involves other offices
(e.g., ORA, OPMA, OQS, OC) as appropriate, based on the inspection findings. In addition, the office that
initiates the for-cause inspection assignment completes the final assessment in 90 days following the close
of the inspection, involving other offices (e.g., ORA, OPMA, OQS, OC) as appropriate. Any follow-up
actions are completed by CDER within 6 months post-inspection.
16
Integration Of FDA Facility Evaluation And Inspection Program For Human Drugs: A Concept Of Operations (ConOps), see
https://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/UCM574362.pdf

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FOOD AND DRUG ADMINISTRATION

COMPLIANCE PROGRAM PROGRAM 7356.002

CHAPTER 56: DRUG QUALITY ASSURANCE

SUBJECT: DRUG MANUFACTURING INSPECTIONS IMPLEMENTATION DATE

Industry codes: 56002 Full Drug Process Inspections (DPI)

PAC Type Subject

Date of Issuance: 10/31/2017 Page 1 of 29

FIELD REPORTING REQUIREMENTS

1 For further information see Part V Regulatory/Administrative Strategy

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5 Food and Drug Administration Safety and Innovation Act (FDASIA),

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PART II- IMPLEMENTATION

• to provide an assessment of firms’ conformance to CGMP requirements for Agency

This program applies to all manufacturing operations at the establishment.

Date of Issuance: 10/31/2017 Page 5 of 29

C. A Scheme of Systems for the Manufacture of Drugs/Drug Products

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See the CGMP regulations, 21 CFR 211 Subparts B, C, D, and J.

Date of Issuance: 10/31/2017 Page 7 of 29

PROGRAM MANAGEMENT INSTRUCTIONS

The Full Inspection Option

The Abbreviated Inspection Option

Selecting Systems for Coverage

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5. Drug Manufacturing Inspection

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PART III – INSPECTIONAL

Inspectional observations noting CGMP deficiencies should be related to a requirement. CGMP

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Specific specialized inspectional guidance may be provided as attachments to this program, or in

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C. System Inspection Coverage

Date of Issuance: 10/31/2017 Page 13 of 29

- Complaint reviews (quality and medical): documented; evaluated; investigated in a timely

- Discrepancy and failure investigations related to manufacturing and testing: documented;

- Change Control: documented; evaluated; approved; need for revalidation assessed

- Product Improvement Projects: for marketed products

- Reprocess/Rework: evaluation, review and approval; impact on validation and stability

- Returns/Salvages: assessment; investigation expanded where warranted; disposition

- Rejects: investigation expanded where warranted; corrective action where appropriate

- Validation: status of required validation/revalidation (e.g., computer, manufacturing

- Training/qualification of employees in quality control unit functions

FACILITIES AND EQUIPMENT SYSTEM

- cleaning and maintenance

Date of Issuance: 10/31/2017 Page 14 of 29

- general air handling systems

- control system for implementing changes in the building

- sanitation of the building, use of rodenticides, fungicides, insecticides, cleaning and

- equipment installation and operational qualification where appropriate

- adequacy of equipment design, size, and location

- equipment surfaces should not be reactive, additive, or absorptive