Download Compliance, Validation, and Related Processes

Premarket Testing and
Validation
Charles Lankford
PharmaSys, Inc.
216 Towne Village Drive
Cary, NC. 27513
[email protected]
PharmaSys, Inc.
www.pharma-sys.com
1
U S. Food and Drug Administration
• Scientific, regulatory, and
public health agency
– oversees items accounting
for 25 cents of every dollar
spent by consumers.
PharmaSys, Inc.
• Jurisdiction
– most food products (other
than meat and poultry)
– human and animal drugs
– therapeutic agents of
biological origin
– medical devices
– radiation-emitting products
for consumer, medical, and
occupational use
– cosmetics
– animal feed
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2
History of the FDA
• single chemist U.S. Department of
Agriculture in 1862
• Regulatory functions added in1906
• The Bureau of Chemistry's name changed to
the Food, Drug, and Insecticide
Administration in July 1927,
– nonregulatory research functions of the bureau
were transferred elsewhere
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3
Events Leading to Formation of
FDA
1905 - Samuel Hopkins Adams :11 articles The Great American Fraud in
Collier's Weekly.
– analyzed the contents of some of the country's most popular medicines.
– argued that many of the companies producing these medicines were
making false claims about their products.
– some cases, these medicines were actually damaging the health of
those people using them
1906 - Upton Sinclair: The Jungle
– fictional portrait of life and death of working class immigrates in turn-ofthe-century Chicago
– filled with page after page of nauseating detail he had researched about
the meat-packing industry
Public demanded sweeping reforms in the food industry
30 June 1906 President Roosevelt signed the Food and Drugs Act, known
simply as the Wiley Act.
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1906 Food and Drugs Act
• Prohibited interstate transport of unlawful food and drugs
under penalty of seizure of the questionable products
and/or prosecution of the responsible parties
• Basis on regulation of product labeling rather than premarket approval
• Drugs, defined in accordance with the standards of
strength, quality, and purity in the United States
Pharmacopoeia and the National Formulary, could not
be sold in any other condition unless the specific
variations from the applicable standards were plainly
stated on the label
PharmaSys, Inc.
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1906 Food and Drugs Act
• Foods were not defined according to analogous
standards, but the law prohibited the addition of any
ingredients that would substitute for the food, conceal
damage, pose a health hazard, or constitute a filthy or
decomposed substance
• If the manufacturer opted to list the weight or measure of
a food, this had to be done accurately
• The food or drug label could not be false or misleading in
any particular, and the presence and amount of eleven
dangerous ingredients, including alcohol, heroin, and
cocaine, had to be listed
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1911
• Supreme Court ruled that the law did not-apply to false therapeutic claims.
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The 1938 Food, Drug, and
Cosmetic Act
• A Tennessee drug company marketed a form of
the new sulfa wonder drug, Sulfanilamide, a
drug used to treat streptococcal infections, that
would appeal to pediatric patients, Elixir
Sulfanilamide.
• 100 people in 15 states died, many were
children
• Dissolved in diethylene glycol, a highly toxic
chemical analogue of antifreeze
• Not tested for toxicity… food and drugs law did
not require safety studies for new drugs
PharmaSys, Inc.
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The 1938 Food, Drug, and
Cosmetic Act
• legally mandated quality and identity
standards for foods
• prohibition of false therapeutic claims for
drugs
• coverage of cosmetics and medical
devices
• clarification of the FDA's right to conduct
factory inspections
• control of product advertising, among
other items
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Kefauver-Harris Amendments
• Thalidomide, chiefly sold and prescribed during the late
1950s and 1960s to pregnant women, as an antiemetic
to combat morning sickness and as an aid to help them
sleep
• Drug stunted the growth of fetal arms and legs, 10,000
babies affected, never approved in US
• Now approved for the treatment of MULTIPLE
MYELOMA and ERYTHEMA NODOSUM LEPROSUM
• Resulted in Kefauver-Harris Amendments
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Kefauver-Harris Amendments
• mandates efficacy & safety before a drug could be marketed
• requires FDA to assess the efficacy of all drugs introduced
since 1938,
• institutes stricter agency control over drug trials (including a
requirement that patients involved must give their informed
consent)
• transferred from the Federal Trade Commission to the FDA
regulation of prescription drug advertising,
• established good manufacturing practices by the drug industry
• granted the FDA greater powers to access company
production and control records to verify those practices
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Drug or Device Deemed
Adulterated if
• If it consists in whole or in part of any
filthy, putrid, or decomposed
substance;
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Drug or Device Deemed
Adulterated if
• prepared, packed, or held under insanitary
conditions
• do not conform to or are not operated or
administered in conformity with current good
manufacturing practice
• are not operated or administered in conformity
with the positron emission tomography
compounding standards and the official
monographs of the United States
Pharmacopoeia
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Drug or Device Deemed
Adulterated if
• composed, in whole or in part, of any
poisonous or deleterious substance
• a color additive which is unsafe
• animal feed bearing or containing a new
animal drug, and such animal feed is
unsafe
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Drug or Device Deemed
Adulterated if
• strength differs from, or its quality or purity
falls below, the standards
• strength, quality, or purity shall be made in
accordance with the tests or methods of
assay set forth in such compendium
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Drug or Device Deemed
Adulterated if
• mixed or packed therewith so as to reduce
its quality or strength or
• substituted wholly or in part
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PART 211 – DRUG GMP
• A--General Provisions
• B--Organization and
Personnel
• C--Buildings and
Facilities
• D--Equipment
• E--Control of
Components and Drug
Product Containers and
Closures
• F--Production and
Process Controls
PharmaSys, Inc.
• G--Packaging and
Labeling Control
• H--Holding and
Distribution
• I--Laboratory Controls
• Subpart J--Records and
Reports
• K--Returned and
Salvaged Drug
Products
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Part 820 – Device QSR
• A--General Provisions
• B--Quality System
Requirements
• C--Design Controls
• D--Document
Controls
• E--Purchasing Controls
PharmaSys, Inc.
•
F--Identification and
Traceability
• G--Production and
Process Controls
• H--Acceptance
Activities
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Part 820 – Device QSR
• I--Nonconforming
Product
• J--Corrective and
Preventive Action
•
• K--Labeling and
Packaging Control
• K--Labeling and
Packaging Control
• N—Servicing
• O--Statistical
Techniques
PharmaSys, Inc.
L--Handling, Storage,
Distribution, and
Installation
• M—Records
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FDA Documentation
• Regulation – Codified and Law
• Preamble – Dialog of FDA’s thinking when
reg was codified
• Guidance - FDA’s current thinking about
reg
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GCP and Clinical Trials
• Electronic Records; Electronic Signatures (21 CFR Part
11)
• Human Subject Protection (Informed Consent) (21 CFR
Part 50)
• Additional Safeguards for Children in Clinical
Investigations of FDA-Regulated Products (Interim Rule)
(21 CFR Part 50, subpart D)
• Financial Disclosure by Clinical Investigators (21 CFR
Part 54)
• Institutional Review Boards (21 CFR Part 56)
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GCP and Clinical Trials
• Forms 1571 (Investigational New Drug Application) and
1572 (Statement of Investigator)
• Applications for FDA Approval to Market a New Drug (21
CFR Part 314)
• Applications for FDA Approval of a Biologic License (21
CFR Part 601)
• Investigational Device Exemptions (21 CFR Part 812)
• Premarket Approval of Medical Devices (21 CFR Part
814
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Drug Approval Process
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Drug Development and Approval
Process
• U.S. system most rigorous in the world
• On average, it costs a company $360 million to get one new
medicine from the laboratory to the pharmacist's shelf
• It takes 12 years on average for an experimental drug to travel from
lab to medicine chest.
• Only five in 5,000 compounds that enter preclinical testing make it to
human testing.
• One of these five tested in people is approved.
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Biological Screening and
Pharmacological Testing
• Studies to explore the pharmacological
activity and therapeutic potential of
compounds.
– animals, isolated cell cultures and tissues,
enzymes and cloned receptor sites as well as
computer models.
•
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Pharmaceutical Dosage
Formulation and Stability Testing
• The process of turning an active
compound into a form and strength
suitable for human use .
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Toxicology and Safety Testing
• Tests to determine the potential risk a
compound poses to man and the
environment
– These studies involve the use of animals,
tissue cultures, and other test systems to
examine the relationship between factors
such as dose level, frequency of
administration, and duration of exposure to
both the short- and long-term survival of living
organisms.
– LD50
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Regulatory Review:
Investigational New Drug (IND)
Application
• An application filed with the U.S. FDA prior to
human testing.
• The IND application is a compilation of all known
information about the compound. It also includes
a description of the clinical research plan for the
product and the specific protocol for phase I
study.
• Unless the FDA says no, the IND is
automatically approved after 30 days and clinical
tests can begin.
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Phase I Clinical Evaluation
• The first testing of a new compound in human
subjects, for the purpose of establishing the
tolerance of healthy human subjects at different
doses
• defining its pharmacologic effects at anticipated
therapeutic levels
• studying its absorption, distribution, metabolism,
and excretion patterns in humans
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Phase II Clinical Evaluation
• Controlled clinical trials of a compound's
potential usefulness and short term risks.
• A relatively small number of patients,
usually no more than several hundred
subjects, enrolled in phase II studies.
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Phase III Clinical Evaluation
• Controlled and uncontrolled clinical trials
of a drug's safety and effectiveness in
hospital and outpatient settings.
– gather precise information on the drug's
effectiveness
– determine adverse effects
– identify the best way of administering and
using
– phase III studies can involve several hundred
to several thousand subjects.
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Institutional Review Boards
•
•
•
•
•
•
used to ensure the rights and welfare of people participating in clinical trials
both before and during their trial participation.
make sure that participants are fully informed and have given their written
consent before studies ever begin.
monitored by the FDA to protect and ensure the safety of participants in
medical research.
An IRB must be composed of no less than five experts and lay people with
varying backgrounds to ensure a complete and adequate review of activities
commonly conducted by research institutions.
In addition to possessing the professional competence needed to review
specific activities, an IRB must be able to ascertain the acceptability of
applications and proposals in terms of institutional commitments and
regulations, applicable law, standards of professional conduct and practice,
and community attitudes.
Therefore, IRBs must be composed of people whose concerns are in
relevant areas.
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Bioavailability Studies
• The use of healthy volunteers to document the rate of
absorption and excretion from the body of a compound's
active ingredients.
• Companies conduct bioavailability studies both at the
beginning of human testing and just prior to marketing to
show that the formulation used to demonstrate safety
and efficacy in clinical trials is equivalent to the product
that will be distributed for sale.
• Companies also conduct bioavailability studies on
marketed products whenever they change the method
used to administer the drug (e.g., from injection or oral
dose form), the composition of the drug, the
concentration of the active ingredient, or the
manufacturing process used to produce the drug.
PharmaSys, Inc.
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Process Development for
Manufacturing and Quality
Control (CMC)
• Engineering and manufacturing design
activities to establish a company's capacity
to produce a product in large volume and
development of procedures to ensure
chemical stability, batch-to-batch
uniformity, and overall product quality.
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Regulatory Review: New Drug
Application (NDA)
• An application to the FDA for approval to market
a new drug. All information about the drug
gathered during the drug discovery and
development process is assembled in the NDA.
• During the review period, the FDA may ask the
company for additional information about the
product or seek clarification of the data
contained in the application.
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Postapproval Research
• Adverse events must be reported
• Additional indications
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Basic Regulatory Requirements for
Medical Devices
• Premarket Notification 510(k), unless
exempt, or Premarket Approval (PMA)
• Establishment registration on form FDA2891
• Medical Device Listing on form FDA-2892
• Quality System (QS) regulation
• Labeling requirements
• Medical Device Reporting (MDR)
PharmaSys, Inc.
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Premarket Notification 510(k) 21 CFR Part 807 Subpart E
• If device requires the submission,
– can not commercially distribute until
you receive a letter of substantial
equivalence from FDA authorizing
you to do so.
PharmaSys, Inc.
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Premarket Notification 510(k) 21 CFR Part 807 Subpart E
• A 510(k) must demonstrate that the device
is substantially equivalent to one legally in
commercial distribution
– Application fee applies to Traditional,
Abbreviated, and Special 510(k)s. Small
businesses may pay smaller fee.
PharmaSys, Inc.
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Premarket Notification 510(k) 21 CFR Part 807 Subpart E
• Most Class I devices and some Class II
devices are exempt
– A list of exempt devices is located at:
http://www.accessdata.fda.gov/scripts/cdrh/cf
docs/cfpcd/315.cfm
PharmaSys, Inc.
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Premarket Approval (PMA) - 21
CFR Part 814
• Product requiring PMAs
– Class III devices, high risk devices, pose a
significant risk of illness or injury
– devices found not substantially equivalent to
Class I and II predicate
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Premarket Approval (PMA) - 21
CFR Part 814
• PMA process is more involved
– includes the submission of clinical data to
support claims made for the device.
– The PMA is an actual approval of the device
by FDA.
• Medical device user fees apply to original
PMAs and certain types of PMA
supplements.
PharmaSys, Inc.
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Investigational Device
Exemption (IDE) - 21CFR Part
812
• Clinical studies with devices of significant
risk must be approved by FDA and by an
Institutional Review Board (IRB) before the
study can begin.
• Studies with devices of nonsignificant risk
must be approved by the IRB only
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Establishment Registration form
FDA-2891 - 21 CFR Part 807
• Manufacturers must register their
establishments with the FDA
• Once a year, FDA sends the registration
form FDA-2891(a) to all registered firms to
be verified, corrected, and returned by the
firm as a yearly registration
• foreign manufacturers must also designate
a U.S. Agent
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Medical Device Listing form
FDA-2892 - 21CFR Part 807
• All medical devices are required to be listed with
the
• Firms that are required to list their devices are
those that:
–
–
–
–
–
–
manufacture,
repackage and relabel,
develop specifications,
reprocess single-use devices,
remanufacture
manufacture accessories and components sold
directly to the end user
PharmaSys, Inc.
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Labeling - 21 CFR Part 801
• Labeling includes labels on the device as
well as descriptive and informational
literature that accompanies the device.
Labeling requirements can be accessed
on the web at:
http://www.fda.gov/cdrh/devadvice/33.html
PharmaSys, Inc.
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Medical Device Reporting - 21
CFR Part 803
• Incidents in which a device may have
caused or contributed to a death or
serious injury must to be reported to FDA
under the Medical Device Reporting
program.
• The MDR regulation is a mechanism for
FDA and manufacturers to identify and
monitor significant adverse events
involving medical devices. The goals of
the regulation are to detect and correct
problems in a timely manner.
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Medical Device Classification
• classifications for approximately 1,700
different generic types of devices
• three regulatory classes based on the
level of control necessary to assure the
safety and effectiveness of the device.
PharmaSys, Inc.
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Device Class and Regulatory
Controls
• Class I General Controls
– With Exemptions
– Without Exemptions
• Class II General Controls and Special
Controls
– With Exemptions
– Without Exemptions
• Class III General Controls and Premarket
Approval
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Class I Devices
• Class I devices are subject to the least regulatory
control.
• They present minimal potential for harm to the user and
are often simpler in design than Class II or Class III
devices.
• Most Class I devices are exempt from the premarket
notification and/or good manufacturing practices
regulation. Information on Class I exempt devices is
located under the heading What are Class I/II
Exemptions?.
PharmaSys, Inc.
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Class I - General Controls
• Class I devices are subject to "General Controls”
–
–
–
–
Establishment Registration (
Medical Device Listing
Manufactured s in accordance with GMP
Labeled in accordance with labeling regulations (21 CFR Part
801 or 809)
– Submission of a premarket notification [510(k)]
Examples of Class I devices include elastic bandages, examination
gloves, and hand-held surgical instruments.
PharmaSys, Inc.
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Class II - Special Controls
• Special controls may include special labeling requirements,
mandatory performance standards and postmarket surveillance.
Examples of Class II devices include sterilizers, LIMS, powered
wheelchairs, infusion pumps, and surgical drapes.
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Class III - Premarket Approval
• Class III is the most stringent regulatory category for
devices.
• insufficient information exists to assure safety and
effectiveness
• Class III devices are usually those that support or
sustain human life
• Premarket approval is required
• Not all Class III devices require an approved PMA.
– Class III devices which are equivalent to devices
legally marketed before May 28, 1976
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Class III Devices Requiring an
Approved Premarket Approval
Application
Examples of Class III devices which require a premarket approval
include replacement heart valves, silicone gel-filled breast implants,
and implanted cerebella stimulators, pacemaker.
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DESIGN VERIFICATION AND
VALIDATION
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DESIGN VERIFICATION
AND VALIDATION
• Establish and maintain procedures for
verifying device design
• Confirm design output meets the design
input requirements
• Results documented in the DHF
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DESIGN VERIFICATION
AND VALIDATION
• Performed under defined operating
conditions on initial production units, lots,
or batches, or their equivalents
• Include testing of production units under
actual or simulated use conditions
• Include software validation and risk
analysis, where appropriate
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DEFINITIONS
• Specification - any requirement with
which a product, process, service, or other
activity must conform
• Validation - confirmation by examination
and provision of objective evidence that
the particular requirements for a specific
intended use can be consistently fulfilled
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DEFINITIONS
• Process Validation - objective evidence that a
process consistently produces a result or
product meeting specifications
• Design Validation - objective evidence that
device specifications conform with user needs
and intended use(s)
• Verification - confirmation by examination and
provision of objective evidence that specified
requirements have been fulfilled
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DESIGN VERIFICATION
AND VALIDATION
• Always done versus specifications
• Control of specifications increases
probability of achieving desired results
• Specifications reviewed before as
development procedes.
• As designs evolve, they should be
evaluated versus their current
specifications.
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DESIGN VERIFICATION
AND VALIDATION
• Always done versus specifications
• Control of specifications increases
probability of achieving desired results
• Specifications reviewed before as
development procedes.
• As designs evolve, they should be
evaluated versus their current
specifications.
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DESIGN VERIFICATION
AND VALIDATION
• Should be done with test equipment
calibrated and controlled according to
quality system requirements.
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DESIGN VERIFICATION
AND VALIDATION
• Performed according to a written
protocol(s)
• Include defined conditions for the testing
• Approved before being used.
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DESIGN VERIFICATION
AND VALIDATION
• Test protocol(s) are not perfect …
• annotate ongoing changes to a protocol
• record technical comments about any
deviations or other events that occurred
during testing
• The slightest problem should not be
ignored
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SOFTWARE
VALIDATION
• Ongoing development - evaluated and
reviewed versus the software
specifications
• “Final" prototype(s) - software and
hardware are validated
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SOFTWARE
VALIDATION
• Before testing detailed code should be
visually reviewed versus flow charts and
specifications.
• All cases, especially decision points and
error/limit handling, should be reviewed
and the results documented.
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SOFTWARE
VALIDATION
• Code visually reviewed versus flow charts
and specifications
• All cases… decision points and error/limit
handling, reviewed and the results
documented
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SOFTWARE
VALIDATION
• Algorithms should checked for accuracy.
– Recalls have occurred because algorithms
were incorrectly copied from a source and, in
other cases, because the source algorithm
was incorrect.
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SOFTWARE VALIDATION
• Testing includes normal operation of the
complete device
• Combined system of hardware and
software should be challenged with
abnormal inputs and conditions. As
appropriate, these inputs and conditions
include such items as
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Inputs and Conditions
• operator errors
• induced failure of
sensors and cables or
other interconnects
• induced failure of
output equipment
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• exposure to static
electricity
• power loss and restart
• simultaneous inputs
or interrupts
• limit testing
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SOFTWARE VALIDATION
• Testing includes normal operation of the
complete device
• Combined system of hardware and
software should be challenged with
abnormal inputs and conditions. As
appropriate, these inputs and conditions
include such items as
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LABELING VERIFICATION
• Exercised such that all labeling, displays,
and outputs are generated, reviewed, and
the results documented.
• All displayed prompts and instructions are
checked versus the manufacturer's and
FDA's labeling requirements and operator
manual.
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LABELING VERIFICATION
• Printed labeling and screen displays
should be checked to see if they are
directed to the user and not to the system
designer
• Data, identifications, or other key
information displayed should be current,
complete, unambiguous, and accurate
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LABELING VERIFICATION
• Printouts should undergo a verification
similar to that performed for the screen or
other displays
• Annotated copies of verified labeling,
printouts, etc. and associated notes and
any checklists should be placed in the
design history file
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§ 820.30(h) Design Transfer
• Each manufacturer shall establish and maintain
procedures to ensure that the device design is
correctly translated into production
specifications.
– Production specifications must ensure that
manufactured devices are repeatedly and reliably
produced within product and process capabilities.
– The process of encapsulating knowledge about the
device into production specifications is critical to
device quality.
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§ 820.30(j) Design history file
• Each manufacturer shall establish and maintain
a DHF for each type of device.
– Other national regulations require some form of
documentation and records. Product documentation
required by Canada, Europe, and Japan contain
certain elements of the U. S. FDA design history file
requirements without requiring all the elements to be
compiled in a file.
– Virtually every section of the design control
requirements specifies information which should be
recorded. The compilation of these records is
sometimes referred to as the design history file.
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Typical DHF
• Detailed design and development plan
specifying design tasks and deliverables.
• Copies of approved design input
documents and design output documents.
• Documentation of design reviews.
• Validation documentation.
• When applicable, copies of controlled
design documents and change control
records.
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Design changes
• establish and maintain procedures for
design changes before their
implementation.
– Document control
– Change control
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Production Testing is not
Verification
• Some manufacturers erroneously equate production
testing with verification.
– Verification testing establishes conformance of design output
with design input
– Production testing is to determine whether the unit under test
has been correctly manufactured… screen out manufacturing
process errors and detect infant mortality failures
• Typically, a small subset of functional and performance
tests accomplish this objective with a high degree of
accuracy.
• Production testing is rarely, if ever, comprehensive
enough to verify the design.
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Example
A leakage test may be used during production to
ensure that a hermetically-sealed enclosure was
properly assembled … may not be sensitive
enough to detect long-term diffusion of gas
through the packaging material.
Permeability of the packaging material is an
intrinsic property of the material rather than an
assembly issue… likely be verified using a more
specialized test than is used during production.
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Environmental Conditions
• Validation should include simulation of the
expected environmental conditions
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VALIDATION DOCUMENTATION
• Validation is a compilation of the results of all
validation activities.
• For a complex design, the detailed results may
be contained in a variety of separate documents
and summarized in a validation report.
• Supporting test articles should be explicitly
referenced in the validation report and either
included as an appendix or available in the
design history file.
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WHAT PROCESSES SHOULD BE
VALIDATED
• Routine end-product tests have insufficient
sensitivity to verify the desired safety and
efficacy of the finished devices
• Clinical or destructive testing would be required
to show that the manufacturing process has
produced the desired result or product
• Routine end-product tests do not reveal all
variations in safety and efficacy that may occur
in the finished devices.
• The process capability is unknown, or it is
suspected that the process is barely capable of
meeting the device specifications.
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§ 820.75 PROCESS VALIDATION
•
(a) Where the results of a process cannot be fully verified by subsequent
inspection and test, the process shall be validated with a high degree of
assurance and approved according to established procedures.
– The validation activities and results, including the date and signature of the
individual(s) approving the validation and where appropriate the major equipment
validated, shall be documented.
•
(b) Each manufacturer shall establish and maintain procedures for
monitoring and control of process parameters for validated processes to
ensure that the specified requirements continue to be met.
– (1) Each manufacturer shall ensure that validated processes are performed by
qualified individual(s).
– (2) For validated processes, the monitoring and control methods and data, the
date performed, and, where appropriate, the individual(s) performing the process
or the major equipment used shall be documented.
•
(c) When changes or process deviations occur, the manufacturer shall
review and evaluate the process and perform revalidation where
appropriate. These activities shall be documented.
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Planning the Process Validation
Study
• The plan should include design reviews.
• The plan for the validation study is documented
in the validation protocol.
• A copy of the protocol and validation results are
placed in the Design History File (DHF) [820.30
(j)] or quality system record file (820.186).
• The operational, monitoring, and other
production-related procedures are part of the
device master record (DMR) (820.181).
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Typical Elements of Process
Validation Study
•
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•
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•
•
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identification of the process
identification of device(s) to be
manufactured using the process
criteria for a successful study
length and duration of the study
assumptions (shifts, operators,
equipment, components;
identification of equipment to be used
in the process [820.75(b)(2)]
identification of utilities for the process
equipment
identification of operators and required
operator qualifications [820.75(b)(2)];
complete description of the process
{may reference the DMR [820.181(b)]};
relevant specifications including those
for the product, components,
manufacturing materials, the
environment, etc. [may reference the
DMR and quality system files
{820.181(a) and (b); 820.186};
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any special controls or conditions to be
placed on preceding processes during
the validation;
process parameters to be controlled and
monitored, and methods for controlling
and monitoring [820.70(a); 820.75(b)(2)];
product characteristics to be monitored
and method for monitoring [820.70(a)(2);
820.75(b)(2); 820.80(c)];
any subjective criteria used to evaluate
the product;
definition of what constitutes
nonconformance for both measurable
and subjective criteria;
statistical methods for data collection and
analysis (820.250);
consideration of maintenance and repairs
[820.72(a)];
conditions that may indicate that the
process should be revalidated
[820.75(c)];
stages of the study where design review
is required; and
approval(s) of the protocol.
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Installation and Operation
Qualification
•
Process equipment should be installed, reviewed, calibrated, challenged, and
evaluated to ensure that it is capable of operating within established limits and
tolerances as well as throughout all anticipated operating ranges.
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examining equipment design and supplied documentation;
determining installation requirements;
establishing any needed environmental controls and procedures;
assuring that the work area has sufficient space to perform the processing and associated
activities;
installing the equipment;
verifying correct installation;
establishing manufacturing procedures for the monitoring, operation, and control of the
equipment including the minimum number of operators;
determining calibration, cleaning, maintenance, adjustment, and expected repair
requirements;
identifying important elements of the equipment that could affect the output or finished
device;
verifying that the system or subsystem performs as intended throughout all anticipated
operating ranges; and
documenting the above information.
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Process Performance
Qualification
• The purpose of process performance qualification is to
rigorously test the process to determine whether it is
capable of consistently producing an output or inprocess or finished devices which meet specifications. In
entering the process performance qualification phase of
validation, it is understood that the:
– device, packaging, and process specifications have been
established, documented, and essentially proven acceptable
through engineering, laboratory or other verification methods
[820.30; 820.70(a)]; and
– process and ancillary equipment and the environment have been
judged acceptable on the basis of installation and operation
qualification studies [820.70(g)].
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Product Performance
Qualification
• Demonstrate that the process has not adversely affected the
finished product and that the product meets its predetermined
specifications and quality attributes.
• Products used for design validation should be manufactured using
the same production equipment, methods and procedures that will
be used in routine production.
• Design validation can be conducted using finished products made
during process validation studies and will satisfy the need for
product performance qualification.
• Design validation shall ensure that devices conform to defined user
needs and intended uses and shall include testing production units
under actual or simulated use conditions [820.30(g)].
• Original designs and design changes are subject to design control
requirements [820.30(i)]. The results of design validation are subject
to review under the design control review requirements [820.30(e)].
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Questions & Answers
• Charles Lankford
• PharmaSys, Inc.
• 216 Towne Village Drive
• Cary, NC. 27513
• [email protected]
integrity… commitment… value… results…
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