documentos fda

Center Name 483 issued

Foods 2496

Devices 817

Drugs 646

Incidental text 303

Bioresearch monitoring 282

Veterinary medicine 232

Biologics 224

Parts 1240 and 1250 169

Human tissue for transplantation 111

Radiological health 16

Special requirements 10

Sum Product Area 483s from System* 5306

Actual Total in system 483s** 4804

Total 483s for Fiscal Year*** 6695

Total number of FY10 inspections 17635

Number of 483 issued from the System*

Inspections ending between 10/1/2009 12:00:00 AM and 9/30/2010 12:00:00 AM

* This table does not represent the complete set of 483's issued

during the fiscal year as some 483's were manually prepared and not

available in this format. The sum of 483's for all Product Areas will

be greater than the actual Total 483's issued during the fiscal year

since a 483 may include citations related to multiple product areas,

and counted more than once, under each relevant product center.

** This is the Actual Total number of 483's issued from this system,

and that are represented in this spreadsheet.

*** This is the count of the total number of 483's issued in and out of

the system during FY2010

Number of 483 issued from the System*

Inspections ending between 10/1/2009 12:00:00 AM and 9/30/2010 12:00:00 AM

Biologics

Center Name Cite Id Ref No ShortDesc

Biologics 76 21 CFR 606.100(b) Maintained and followed

98 21 CFR 606.100(c) Thorough investigations

160 21 CFR 606.160(a)(1) Person performing, test results,

interpretation

155 21 CFR 606.160(b) Required records

154 21 CFR 606.160(a)(1) Concurrent documentation

9225 21 CFR 606.171 Biological product deviation report

31 21 CFR 606.20(b) Qualifications of responsible

personnel

4425 21 CFR 606.60(a) Equipment observed,

standardized, calibrated

159 21 CFR 606.160(a)(1) Legibility and indelibility

67 21 CFR 606.65(e) Following manufacturer's

instructions

78 21 CFR 606.100(c) Record review prior to release

57 21 CFR 606.60(a) Maintain and clean equipment

Page 3

Biologics

12202 21 CFR 606.170(a) Adverse Reaction - Investigations

15030 21 CFR 606.60(b) Equipment calibration frequency

41 21 CFR 606.40(a)(1) Provide space for examination

158 21 CFR 606.160(e) Unsuitable donors

89 21 CFR 606.100(b)(10) Controlling storage temperatures

208 21 CFR 640.3(a)(1) Donor suitability procedures not

followed

9044 21 CFR 600.10(b) Personnel capabilities

9220 21 CFR 606.100(b)(20) Donor notification

12203 21 CFR 606.170(a) Adverse Reaction- Reports of

Investigations

61 21 CFR 606.60(a) Provide proper equipment to meet

requirements

224 21 CFR 640.4(f) Arm preparation

9243 21 CFR 630.6(a) Notification

35 21 CFR 606.40 Clean & orderly

80 21 CFR 606.100(b)(1) Donor criteria

161 21 CFR 606.160(a)(2) Determination of lot numbers and

supplies

Page 4

Biologics

9234 21 CFR 630.6(c) Notification w/in 8 weeks

63 21 CFR 606.65 Safe, sanitary, orderly storage

142 21 CFR 606.140(a) Establishment of spec., standards,

and test procedures

150 21 CFR 606.151(e) Procedures to maintain records of

emergency transfusions

157 21 CFR 606.160(d) Retention period

212 21 CFR 640.3(b)(3) Qualifications of donor -

hemoglobin

227 21 CFR 640.4(h) Storage temperatures after

collection

246 21 CFR 640.25(a) Storage temps./agitation

9089 21 CFR 600.14(c) When to report

9219 21 CFR 606.100(b)(20) Donor deferral

42 21 CFR 606.40(a)(2) Provide space for blood withdrawal

50 21 CFR 606.40(c) Provide adequate handwashing

51 21 CFR 606.40(c) Provide adequate toilet facilities

54 21 CFR 606.40(d)(2) Provide adequate disposal of blood

& blood components

77 21 CFR 606.100(b) Written SOPs available for use by

personnel

Page 5

Biologics

88 21 CFR 606.100(b)(9) Written methods for investigating

adverse reactions

93 21 CFR 606.100(b)(14) QC procedures for supplies and

reagents

94 21 CFR 606.100(b)(15) Schedules and procedures for

equipment & calibration

117 21 CFR 606.121(f) Labeling of blood products

unsuitable for transfusion

156 21 CFR 606.160(c) Assignment of donor number

165 21 CFR 606.170(a) Adverse reaction - Maintenance of

Reports

236 21 CFR 640.5(e) Testing - inspection

251 21 CFR 640.25(b) Quality control

333 21 CFR 640.64(e) Prevention of contamination

376 21 CFR 640.120 Alternative procedures

3244 21 CFR 640.61 Written consent

9052 21 CFR 600.11(b) Equipment

9227 21 CFR 606.171(a) BPDR - procedures

9236 21 CFR 630.6(b)(1) Deferred or not suitable

Page 6

Biologics

9238 21 CFR 630.6(b)(3) Results of testing

9241 21 CFR 630.6(a) Supplemental results

43 21 CFR 606.40(a)(3) Provide space for storage of blood

& blood products

45 21 CFR 606.40(a)(5) Provide space for storage of

finished product

49 21 CFR 606.40(a)(9) Provide space for all packaging,

labeling, & finishing ops.

64 21 CFR 606.65(b) Visual examination

75 21 CFR 606.100(a) SOP compliance

81 21 CFR 606.100(b)(2) Donor qualifying tests &

measurements

105 21 CFR 606.122 Instruction circular - required

information

121 21 CFR 606.121(c)(2) Name, address, registration

number

137 21 CFR 606.121(c)(13) Unapproved encoded/machine

readable information

147 21 CFR 606.151(d) Crossmatching of donor/recipient

cells

162 21 CFR 606.165(a) Distribution and receipt - recalls

164 21 CFR 606.165(c) Receipt records - content

Page 7

Biologics

167 21 CFR 606.170(b) Adverse reaction - fatality

198 21 CFR 640.2(c)(3) Blood not stored between 1-6 deg /

shipped 1-10 deg

205 21 CFR 640.3(f) Donations in less than eight weeks

215 21 CFR 640.3(b)(6) Qualifications of donor - disease

transmissible by blood

225 21 CFR 640.4(f) Closed system

233 21 CFR 640.5(b) Testing - ABO

247 21 CFR 640.24(b) Storage until removal of platelets

255 21 CFR 640.31 Donor suitability

270 21 CFR 640.34(b) Fresh Frozen Plasma - preparation

272 21 CFR 640.34(b) Fresh Frozen Plasma - storage

requirements

325 21 CFR 640.63(c)(10) Narcotics use

335 21 CFR 640.65(b)(1)(i) Serological test

369 21 CFR 640.72(a)(1) Shipping temperature requirements

3252 21 CFR 640.63(a) Determination not made on day of

collection

Page 8

Biologics

3258 21 CFR 640.63(d) Unreliable answers

3443 21 CFR 610.47 Notification of transfusion

recipients

9051 21 CFR 600.11(a) Work areas - temperatures

9076 21 CFR 600.12(a) Maintenance - concurrence

9077 21 CFR 600.12(a) Maintenance - completeness

9080 21 CFR 600.12(b)(2) Retention - Records of Recall

9086 21 CFR 600.14(a)(1) Who must report - manufacturer

9092 21 CFR 600.80(b) Review of Adverse Experiences -

follow up information

9107 21 CFR 600.11(h) Sterile & pyrogen free

9223 21 CFR 606.160(b)(6) Required records - transfusion

reaction and complaints

9235 21 CFR 630.6(c) Documentation

9237 21 CFR 630.6(b)(2) Type of donations

9240 21 CFR 630.6(d)(1) Physician notification

Page 9

Biologics

9242 21 CFR 630.6(d)(2) Notification

9271 21 CFR 610.41 Donor Deferral - reentry

9596 21 CFR 640.3(a) Donor suitability by means of

medical history

Page 10

Biologics

LongDesc Frqncy

Written standard operating procedures including all steps to be followed in the

[collection] [processing] [compatibility testing] [storage] [distribution] of blood and

blood components for [homologous transfusion] [autologous transfusion] [further

manufacturing purposes] are not always [maintained] [followed] [maintained on

the premises]. Specifically, ***

111

Failure to [perform a thorough investigation] [make a record of the conclusions

and follow-up] of [an unexplained discrepancy] [a failure of a lot or unit to meet

any of its specifications]. Specifically,***

37

Records fail to [identify the person performing the work] [include dates of the

various entries] [show test results] [include interpretation of the results] [show the

expiration date assigned to specific products] [be as detailed as necessary] so as

to provide a complete history of the work performed. Specifically, ***

26

Failure to maintain [donor] [processing] [storage and distribution] [compatibility

testing] [quality control] [general] records. Specifically, ***

24

Records are not concurrently maintained with the performance of each significant

step in the [collection] [processing] [compatibility testing] [storage] [distribution] of

each unit of blood and blood components so that all steps can be clearly traced.

Specifically, ***

23

Failure to submit a biological product deviation report [within 45 days from the

date you acquired information suggesting that a reportable event occurred].

Specifically, ***

23

The personnel responsible for the [collection] [processing] [compatibility testing]

[storage] [distribution] of blood or blood components are not adequate in [number]

[educational background] [training and experience, including professional training

as necessary] to assure competent performance of their assigned functions, and

to ensure that the final product has the safety, purity, potency, identity and

effectiveness it purports or is represented to possess. Specifically, ***

20

Equipment used in the [collection] [processing] [compatibility testing] [storage and

distribution] of blood and blood components is not [observed] [standardized]

[calibrated] on a regularly scheduled basis as prescribed in the SOP Manual.

Specifically, ***

15

Records are [illegible] [not indelible]. Specifically, *** 13

Failure to use supplies and reagents in a manner consistent with instructions

provided by the manufacturer. Specifically, ***

12

All records pertinent to a lot or unit were not reviewed before the release or

distribution of a lot or unit of final product. Specifically, ***

12

Failure to [maintain] [locate] equipment used in the [collection] [processing]

[compatibility testing] [storage] [distribution] of blood and blood products [in a

clean and orderly manner] [so as to facilitate cleaning and maintenance].

Specifically, ***

9

Page 11

Biologics

A thorough investigation of each reported adverse reaction was not made.

Specifically,

9

Equipment used in the [collection][processing][compatibility testing][storage and

distribution] of blood and blood components is not observed, standardized and

calibrated with at least the frequency required. Specifically, ***

9

Failure to provide adequate space for [private] [accurate] examinations of

individuals to determine their suitability as blood donors. Specifically, ***

7

A record is not available from which unsuitable (deferred) donors may be

identified so that products from such individuals will not be distributed.

Specifically, ***

7

The standard operating procedure fails to include a written description of the

storage temperatures and methods of controlling storage temperatures for all

blood products and reagents Specifically, ***

6

Failure to [follow] [maintain] [maintain on the premises] standard procedures and

methods for determining the suitability of a donor as a source of blood.

Specifically, ***

6

Failure to assure that personnel have [capabilities commensurate with] [the

necessary training in] [necessary experience in] [a thorough understanding of] the

operations which they perform. Specifically, ***

6


[donor notification process] [process for follow-up if the initial attempt at donor

notification fails]. Specifically, ***

6

Written reports of investigations of adverse reactions, including conclusions and

follow up, are not prepared and maintained. Specifically,

6

Failure of equipment to perform in the manner for which it was designed so as to

assure compliance with the official requirements prescribed in 21 CFR 606.

Specifically, ***

5

The phlebotomy site is not prepared by a method that gives maximum assurance

of a sterile container of Whole Blood. Specifically, ***

5

Failure to make reasonable attempts to notify a donor who has been [deferred

based on the results of tests for evidence of communicable disease agent(s)]

[determined not be to suitable as a donor based on suitability criteria].

Specifically, ***

5

Failure to maintain facilities in a clean and orderly manner. Specifically, *** 4

The standard operating procedure fails to include written descriptions of criteria

used to determine donor suitability, including acceptable medical history criteria.

Specifically, ***

4

Appropriate records are not available to determine the lot numbers of [supplies]

[reagents] used for specific [lots] [units] of the final product. Specifically, ***

4

Page 12

Biologics

Failure to make reasonable attempts to notify the donor within 8 weeks after

determining that the donor is deferred or determined not to be suitable for

donation. Specifically, ***

4

Failure to store all supplies and reagents used in the [collection] [processing]

[compatibility testing] [storage] [distribution] of blood and blood components in a

safe, sanitary and orderly manner. Specifically, ***

3

Failure to establish scientifically sound and appropriate specifications, standards

and test procedures to assure that blood and blood components are safe, pure,

potent and effective. Specifically, ***

3

Records [including signature by the physician requesting the procedure] are not

maintained of all emergency transfusions [including complete documentation

justifying the emergency action]. Specifically, ***

3

Failure to retain records [for 5 years after the records of processing have been

completed] [for 6 months after the latest expiration date for the individual product]

[indefinitely where there is no expiration date]. Specifically, ***

3

Each donor was not in good health as indicated in part by the blood hemoglobin

level which was demonstrated to be less than 12.5 gm. of hemoglobin per 100 ml

of blood (38% by microhematocrit). Specifically, ***

3

After collection, blood is not [immediately stored at a temperature between 1 and

6 degrees Celsius] [transported from the donor clinic to the processing laboratory

in temporary storage to cool the blood continuously toward a range between 1

and 6 degrees Celsius]. Specifically, ***

3

Failure to store platelets immediately after resuspension [at 20 to 24 degrees

Celsius with continuous gentle agitation] [at 1 to 6 degrees Celsius]. Specifically,

***

3

Biological product deviations [were] [are] not reported within the 45 calendar day

timeframe. Specifically, ***

3


donor deferral process. Specifically, ***

3

Failure to provide adequate space for the withdrawal of blood from donors with

minimal [risk of contamination] [exposure to activities and equipment unrelated to

blood collection]. Specifically, ***

2

Failure to provide [adequate] [clean] [convenient] handwashing facilities for

personnel. Specifically, ***

2

Failure to provide [adequate] [clean] [convenient] toilet facilities for donors and

personnel. Specifically, ***

2

Failure to provide for safe and sanitary disposal for blood and blood components

not suitable for use or distribution. Specifically, ***

2

Failure to make available written procedures for use by personnel in the areas

where the procedures are performed. Specifically, ***

2

Page 13

Biologics


procedures for investigating adverse donor and recipient reactions. Specifically,

***

2


quality control procedures for supplies and reagents employed in [blood

collection] [processing] [pretransfusion testing]. Specifically, ***

2

The standard operating procedure fails to include a written description of

schedules and procedures for equipment maintenance and calibration.

Specifically, ***

2

Failure to prominently label blood and blood components (except for recovered

plasma) determined to be unsuitable for transfusion with ["NOT FOR

TRANSFUSION"] [the reason the unit is considered unsuitable]. Specifically, ***

2

Failure of records describing the history and ultimate disposition of blood products

to include a donor number [assigned to each accepted donor] [which relates to

the unit of blood collected from that donor] [which relates to the donor's medical

record] [which relates to any component or blood product from the donor's unit of

blood]. Specifically, ***

2

Failure to maintain reports of complaints of adverse reactions regarding each unit

of blood or blood product arising as a result of [blood collection] [transfusion].

Specifically, ***

2

Failure to [visually inspect blood during storage and immediately prior to issue for]

[prevent issuance of blood found to have] abnormal color, physical appearance,

or indication or suspicion of microbial contamination. Specifically, ***

2

Failure to test each month (of manufacture) four units prepared from different

donors at the end of the storage period for [platelet count] [pH of not less than 6.0

measured at the storage temperature of the unit] [actual plasma volume].

Specifically, ***

2

The phlebotomy site is not prepared by a method that gives maximum assurance

of a sterile container of blood. Specifically, ***

2

Failure to request from CBER and obtain approval for exceptions or alternatives

to requirements regarding [blood] [blood components] [blood products].

Specifically, ***

2

Failure to obtain written consent of prospective Source Plasma donors.

Specifically, ***

2

There is no assurance that equipment is [adequately sterilized] [properly cleaned]

[inspected for cleanliness] [suitable for use]. Specifically, ***

2

Failure to establish a procedure to obtain information about [deviations]

[complaints] [adverse events] from your contractor. Specifically, ***

2

Failure to notify the donor [that the donor is deferred or determined not to be

suitable] [of the reason for deferral]. Specifically, ***

2

Page 14

Biologics

Failure to notify the donor of the results of [tests for evidence of infection due to

communicable disease agents that were a basis for deferral] [supplemental tests].

Specifically, ***

2

Failure to [attempt to obtain the results of supplemental testing prior to notifying a

donor of a deferral] [notify a donor of the results of supplemental testing].

Specifically, ***

2

Failure to provide adequate space for the storage of blood or blood components

pending completion of tests. Specifically, ***

1

Failure to provide adequate space for the storage of finished products prior to

distribution. Specifically, ***

1

Failure to provide adequate space for the orderly conduction of all [packaging]

[labeling] [other finishing] operations. Specifically, ***

1

Failure to inspect each blood collecting container [and its satellite container(s)] for

damage or evidence of contamination including breakage of seals and abnormal

discoloration [prior to its use] [immediately after filling]. Specifically, ***

1

Failure of the Standard Operating Procedure to comply with additional standards

in 21 CFR 640. Specifically, ***

1

The standard operating procedure fails to include written descriptions of methods

for performing donor qualifying tests and measurements, including minimum and

maximum values for a test or procedure when a factor in determining

acceptability. Specifically, ***

1

Failure to provide an instruction circular for products intended for transfusion

containing adequate directions for use and the information contained in 21 CFR

606.122. Specifically, ***

1

The container label fails to include the [name] [address] [registration number] [the

license number of each manufacturer, for a licensed product]. Specifically, ***

1

The container label bears encoded information in the form of machine-readable

symbols which have not been approved for use by the Director, Center for

Biologics Evaluation and Research). Specifically, ***

1

Failure of standard operating procedures for compatibility testing to include the

testing of the donors cells with the recipients serum (minor crossmatch) by a

method that will demonstrate agglutinating, coating and hemolytic antibodies.

Specifically, ***

1

Failure of distribution and receipt procedures to include a system by which the

distribution or receipt of each unit can be readily determined to facilitate its recall.

Specifically, ***

1

Receipt records fail to contain the [name and address of the collecting facility]

[date received] [donor or lot number assigned by the collecting facility] [date of

expiration or the date of collection, whichever is applicable] Specifically, ***

1

Page 15

Biologics

A confirmed, fatal complication of [blood collection] [transfusion] was not

[reported as soon as possible] [submitted in writing within 7 days after the fatality]

to the Director, Office of Compliance, Center for Biologics Evaluation and

Research by the [collecting facility in the event of a donor reaction] [facility that

performed the compatibility tests in the event of a transfusion reaction].

Specifically, ***

1

Reissued blood has not been [stored continuously at 1 to 6 C] [shipped between 1

and 10 C]. Specifically, ***

1

A person served as a source of blood more than once in 8 weeks and was not

examined at the time of donation and certified by a physician to be in good health

as indicated in part in 21 CFR 640.3(b). Specifically, ***

1

Failure to determine whether each donor is free from any disease transmissible

by blood as determined by history and examinations. Specifically, ***

1

The blood is [not collected by aseptic methods in a sterile system] [collected

using a vented system which fails to protect the blood against contamination].

Specifically, ***

1

Failure to test blood for determination of ABO blood group [using two blood group

tests] [using appropriate reagents] [using appropriate techniques]. Specifically,

***

1

Failure to hold [whole blood] [plasma] immediately after collection between 20

and 24 degrees Celsius until the platelets are separated. Specifically, ***

1

Failure to ensure that [whole blood] [plasmapheresis] donors meet suitability

criteria. Specifically, ***

1

Failure to prepare Fresh Frozen Plasma [from blood collected by a single

uninterrupted venipuncture] [separated from the red blood cells, placed in a

freezer within the appropriate time frame, and stored at - 18 degrees Celsius or

colder]. Specifically, ***

1

Failure to place plasma, separated from red blood cells and intended to be

labeled Fresh Frozen Plasma, in a freezer within eight hours after phlebotomy at

a temperature of -18 degrees Celsius or colder. Specifically, ***

1

Each donor was not in good health on the day of donation, as indicated in part by

[arms] [forearms] with [skin punctures] [scars] indicative of addiction to self-

injected narcotics. Specifically, ***

1

Failure to draw from each donor [on the day of the first medical exam or

plasmapheresis] [at least every 4 months] a sample of blood tested for [syphilis]

[total plasma or serum protein determination] [serum protein electrophoresis or

equivalent test]. Specifically, ***

1

Failure to maintain documentation establishing that the shipping temperature

requirements are being met for Source Plasma intended for manufacture into

injectable products. Specifically, ***

1

Determination of the suitability of Source Plasma donors was not made on the

day of collection. Specifically, ***

1

Page 16

Biologics

Failure to consider as unsuitable any donor who does not appear to be providing

reliable answers to medical history questions. Specifically, ***

1

Failure to [notify the attending physician of a recipient of a lookback unit] [make a

minimum of three attempts within 8 weeks to notify the recipient of a lookback unit

in the event the physician does not inform the recipient] [notify recipient's legal

representative or relative] [document notifications of lookback units]. Specifically,

***

1

The [refrigerators] [incubators] [temperature controlled rooms] [are not maintained

at the required temperatures] [are not free of extraneous material that may affect

the safety of the product]. Specifically, ***

1

Records are not made [concurrently with the performance] of each step in the

[manufacture] [distribution] of products. Specifically, ***

1

The [manufacturing] [distribution] records [are not legible and indelible] [do not

detail the various steps of manufacture of the product]. Specifically, ***

1

Recall records for distributed product [were] [are] not [generated] [retained]

[complete]. Specifically, ***

1

Failure to submit [a] biological deviation [report] [reports]. Specifically, *** 1

Failure to submit all follow up information on adverse experience reports to FDA,

as required. Specifically, ***

1

There is no assurance that [final containers] [closures] for products intended for

use by injection are [sterile] [pyrogen free]. Specifically, ***

1

Failure to maintain records of transfusion reaction reports and complaints,

including investigation and follow up. Specifically, ***

1

Failure to [document that you have successfully notified a deferred donor]

[document that you have made reasonable attempts to notify a deferred donor].

Specifically, ***

1

Failure to notify the donor of the types of donations of blood or blood components

that the donor should not donate in the future. Specifically, ***

1

Failure to provide to an autologous donor's referring physician [information that

the autologous donor is deferred based on the results of tests for evidence of

infection due to communicable disease agents, and the reason for that decision]

[the types of donation of blood and blood components that the autologous donor

should not donate in the future] [the results of tests for evidence of infection due

to communicable disease agent(s) that were a basis for deferral] [results of any

supplemental tests]. Specifically, ***

1

Page 17

Biologics

Failure to [make] [document] reasonable attempts to notify the autologous donor's

referring physician within 8 weeks after determining that the autologous donor is

deferred. Specifically, ***

1

The method or process used to requalify deferred donors was not found

acceptable for such purposes by FDA. Specifically, ***

1

Failure to [always] determine donor suitability on the day of collection by means of

[medical history] [test for hemoglobin level] [physical examination]. Specifically,

***

1

Page 18

BIMO


Bioresearch monitoring 7560 21 CFR 312.60 FD-1572, protocol compliance

7530 21 CFR 312.62(b) Case history records- inadequate or

inadequate

7281 21 CFR 56.108(a)(1) Initial and continuing reviews

7526 21 CFR 312.62(a) Accountability records

7318 21 CFR 56.115(a)(2) Minutes of IRB meetings

7227 21 CFR 50.27(a) Consent form not

approved/signed/dated

7334 21 CFR 56.115(a)(5) List of members

7498 21 CFR 312.66 Unanticipated problems

7562 21 CFR 312.60 Informed consent

Page 19

BIMO

7290 21 CFR 56.108(c) Members present for review

7321 21 CFR 56.110(c) Method to keep members advised

7482 21 CFR 312.50 General responsibilities of sponsors

7335 21 CFR 56.115(a)(6) Written procedures per 56.108(a) and

(b)

7552 21 CFR 312.66 Changes in research

7520 21 CFR 312.64(b) Safety reports

7231 21 CFR 50.20 Consent not obtained, exceptions do

not apply

7278 21 CFR 56.107(e) Conflict of interest

7342 21 CFR 56.108(b)(2) Prompt reporting of noncompliance

7391 21 CFR 50.25(a)(5) Confidentiality, FDA inspection of

records

Page 20

BIMO

7286 21 CFR 56.108(b)(1) Prompt reporting of unanticipated

problems

7293 21 CFR 56.109(f) Continuing review

7343 21 CFR 56.108(b)(3) Reporting of suspension/termination

7480 21 CFR 312.50 Ensuring compliance with plan and

protocol

7654 21 CFR 56.110(b) Research not eligible for expedited

review

7411 21 CFR 312.53(c)(1) Investigator statement (FDA 1572)

7517 21 CFR 312.66 Initial and continuing review

7392 21 CFR 50.25(a)(7) Whom to contact

7209 21 CFR 50.25(a)(1) Procedures, identification of those

which were experimental

7277 21 CFR 56.107(d) One non-affiliate member

7368 21 CFR 56.108(a)2) More frequent reviews, verification of

no changes

Page 21

BIMO

7459 21 CFR 312.57(a) Records of receipt, shipment,

disposition

3923 21 CFR 58.33(f) Study director: transfer of data to

archives

4007 21 CFR 58.130(a) Conduct: in accordance with protocol

4025 21 CFR 58.185(a)(9) Final report: circumstances affecting

data qual., integrity

7316 21 CFR 56.115(a)(4) Copies of IRB/CI correspondence

7333 21 CFR 56.104(c) Emergency use and IRB approval

7369 21 CFR 56.109(h) Children as subjects

7371 21 CFR 56.108(a)(1) Reporting findings and actions to

investigator/institution

7666 21 CFR 50.20 Understandable language

3920 21 CFR 58.33(c) Study director: unforeseen

circumstances

3926 21 CFR 58.35(b)(1) QAU: maintain a master schedule

Page 22

BIMO

3932 21 CFR 58.35(b)(6) QAU: review final study report

3989 21 CFR 58.107 Test article: handling

4006 21 CFR 58.120(b) Protocol: approval of changes

7305 21 CFR 56.110(b)(2) Minor changes

7319 21 CFR 56.115(a)(3) Records of continuing review

7337 21 CFR 56.115(b) Retention of records

7339 21 CFR 56.108(a)(4) Changes in approved research

7340 21 CFR 56.108(a)(3) Prompt reporting of changes

7388 21 CFR 50.25(a)(2) Reasonably foreseeable risks or

discomforts

7390 21 CFR 50.25(a)(4) Alternate procedures, courses of

treatment

Page 23

BIMO

7393 21 CFR 50.25(a)(8) Participation; refusal and

discontinuance

7657 21 CFR 50.25(b)(5) Significant new findings

3909 21 CFR 58.31(a) Management: designating the study

director

3918 21 CFR 58.33(a) Study director: follow study protocol

3919 21 CFR 58.33(b) Study director: all data recorded and

verified

3922 21 CFR 58.33(e) Study director: follow GLP regulations

3952 21 CFR 58.61 Equipment: appropriate design and

adequate capacity

3954 21 CFR 58.63(a) Equipment: calibration

3958 21 CFR 58.81(a) SOPs: authorization and

documentation of deviations

3959 21 CFR 58.81(a) SOPs: authorized changes

Page 24

BIMO

3960 21 CFR 58.81(b) SOPs: required

4016 21 CFR 58.185(a) Final report: non-existent

7274 21 CFR 56.107(a) At least five members with varying

backgrounds

7279 21 CFR 56.107(f) Invited individual allowed to vote with

IRB

7297 21 CFR 56.109(b) Information given to subjects

7317 21 CFR 56.115(a)(1) Copies of all research proposals and

related documents

7353 21 CFR 50.52 Factors required for approval

Page 25

BIMO

7363 21 CFR 50.55(f) Documentation of permission by

parents or guardian

7370 21 CFR 56.111(c) Children as subjects

7384 21 CFR 50.25(b)(1) Statement of risks

7387 21 CFR 50.25(a)(1) Statement of research, purpose,

duration of participation

7406 21 CFR 56.109(a) Scope of reviews

7479 21 CFR 312.56(a) Monitoring investigations

7488 21 CFR 312.59 Records of unused drug disposition

7527 21 CFR 312.62(a) Unused drug disposition (investigator)

7531 21 CFR 312.62(c) Record retention

7543 21 CFR 312.61 Unauthorized recipients (investigator)

7656 21 CFR 56.108(c) Approval from a majority of members

present

Page 26

BIMO

7664 21 CFR 50.20 Circumstances of obtaining consent

3900 21 CFR 58.10 Notifying contractor of GLP status

3902 21 CFR 58.29(a) Personnel: education, training,

experience

3911 21 CFR 58.31(c) Management: assure there is a QAU

3913 21 CFR 58.31(e) Management: availability of resources

3915 21 CFR 58.31(g) Management: QAU findings to study

director

3925 21 CFR 58.35(a) QAU: separate and independent

3931 21 CFR 58.35(b)(5) QAU: authorize deviations from

protocols or SOPs

3933 21 CFR 58.35(b)(7) QAU: signed statement in final report

3935 21 CFR 58.35(d) QAU: access to SOPs, certify

inspections

3945 21 CFR 58.45 Facility: perishable supplies

Page 27

BIMO

3949 21 CFR 58.47(b) Facility: article storage separate from

test system

3955 21 CFR 58.63(b) Equipment: maintenance SOPs

3957 21 CFR 58.81(a) SOPs: laboratory methods

3976 21 CFR 58.90(f) Animal care: cage and equipment

cleaning

3977 21 CFR 58.90(g) Animal care: analysis of feed and

water

3983 21 CFR 58.105(a) Test article: characterization

3996 21 CFR 58.120(a)(3) Protocol: sponsor name and address

4008 21 CFR 58.130(b) Conduct: test systems monitoring

4011 21 CFR 58.130(e) Conduct: recording in ink

4013 21 CFR 58.130(e) Conduct: changes not obscuring

original entries

4018 21 CFR 58.185(a)(2) Final report: objectives, procedures,

changes

4021 21 CFR 58.185(a)(5) Final report: stability of test and

control articles

Page 28

BIMO

4024 21 CFR 58.185(a)(8) Final report: dosage, regimen, route of

admin., duration

4028 21 CFR 58.185(a)(12) Final report: reports of individual

scientists

4039 21 CFR 58.190(c) Archives: individual responsible

4041 21 CFR 58.190(e) Archives: indexing, expedient retrieval

4045 21 CFR 58.195(e) Archives: retention of summaries of

training, et. al.

4047 21 CFR 58.195(g) Archives: records not retained as

originals, true copies

7270 21 CFR 56.103(a) IRB review requirement

7276 21 CFR 56.107(c) One scientific and one non-scientific

member

7292 21 CFR 56.109(g) Providing publicly-disclosed

information to sponsor

7320 21 CFR 56.109(e) IRB approvals/disapprovals - general

7322 21 CFR 56.111 (a)(2) Risks to subjects reasonable

7325 21 CFR 56.111(a)(5) Informed consent documented

Page 29

BIMO

7328 21 CFR 56.111(b) Vulnerable subject safeguards

7336 21 CFR 56.115(a)(7) Statements of significant new findings

7354 21 CFR 50.53 Factors required for approval

7374 21 CFR 56.109(c)(2) Exception from informed consent;

emergency research

7389 21 CFR 50.25(a)(3) Benefits to the subject

7394 21 CFR 50.24(a)(2) No determination that obtaining IC

wasn't feasible

Page 30

BIMO

7396 21 CFR 50.24(a)(3) Prospect of direct benefit not

determined

7398 21 CFR 50.24(a)(6) No determination that IC

procedure/document were approved

7399 21 CFR 50.24(a)(7) Additional protections of rights and

welfare

7410 21 CFR 312.53(a) Investigator selection

7428 21 CFR 312.53(c)(2) Investigator CV or other statement of

qualifications

7452 21 CFR 312.56(c) IND safety report

Page 31

BIMO

7453 21 CFR 312.56(b) Investigator non-compliance

7507 21 CFR 312.52(a) Transfer of obligations

7519 21 CFR 312.64(c) Final study report

7534 21 CFR 312.68 FDA access to clinical investigator

records

7545 21 CFR 312.120(c) Foreign clinical trials

7555 21 CFR 312.53(d) Selecting monitors

7557 21 CFR 312.56(b) Notification of FDA of termination of

investigator

7558 21 CFR 312.57(c) Record retention requirement

7629 21 CFR 312.56(c) Annual report

7631 21 CFR 312.53(c)(4) Financial information - commitment to

update

7638 21 CFR 312.20(a) Failure to submit an IND

Page 32

BIMO

7652 21 CFR 56.113 Reporting

7660 21 CFR 50.24(a)(1) IRB failed to find/document required

conditions

7679 21 CFR 56.106(a) IRB for CI's in support of

research/marketing permits

Page 33

BIMO

LongDesc Frqncy

An investigation was not conducted in accordance

with the [signed statement of investigator]

[investigational plan]. Specifically***

123

Failure to prepare or maintain [adequate] [accurate]

case histories with respect to [observations and data

pertinent to the investigation] [informed consent].

Specifically, ***

75

The IRB [has no] [did not follow its] written

procedure for conducting its [initial] [continuing]

review of research. Specifically, ***

36

Investigational drug disposition records are not

adequate with respect to [dates] [quantity] [use by

subjects]. Specifically, ***

36

Minutes of IRB meetings have not been [prepared]

[maintained] in sufficient detail to show [attendance

at the meetings] [actions taken by the IRB] [the vote

on actions, including the number of members voting

for, against and abstaining] [the basis for requiring

changes in or disapproving research] [a written

summary of the discussion of controverted issues

and their resolution]. Specifically, ***

33

Informed consent was not properly documented in

that the written informed consent used in the study

[was not approved by the IRB] [was not signed by

the subject or the subjects legally authorized

representative at the time of consent ] [was not

dated by the subject or the subject's legally

authorized representative at the time of consent].

Specifically, ***

27

A list of IRB members has not been [prepared]

[maintained], identifying members by [name] [earned

degrees] [representative capacity] [indications of

experience sufficient to describe each member's

chief anticipated contribution to IRB deliberations]

[any employment or other relationship between each

member and the institution]. Specifically, ***

20

Failure to report promptly to the IRB all

unanticipated problems involving risk to human

subjects or others. Specifically, ***

19

Failure to obtain informed consent in accordance

with 21 CFR Part 50 from each human subject prior

to [drug administration] [conducting study-related

tests] . Specifically***

18

Page 34

BIMO

For other than expedited reviews, the IRB does not

always review proposed research at convened

meetings at which a majority of the members of the

IRB are present, including at least one member

whose primary concerns are in nonscientific areas.

Specifically, ***

16

The IRB uses an expedited review procedure, but

[has not adopted] [is not following] a method for

keeping members advised of research proposals

which have been approved under the procedure.

Specifically, ***

16

Failure to [select qualified investigators] [provide

investigators with the information needed to conduct

the study properly] [ensure proper monitoring of the

study] [ensure the study is conducted in accordance

with the protocol and/or investigational plan] [ensure

that FDA and all investigators are promptly informed

of significant new adverse effects or risks].

Specifically, ***

15

Documentation has not been [prepared]

[maintained] of written procedures for the IRB, as

required by 21 CFR 56.108(a) and (b). Specifically,

***

13

Not all changes in research activity were approved

by an Institutional Review Board prior to

implementation. Specifically, ***

13

Failure to report [promptly] to the sponsor adverse

effects that may reasonably be regarded as caused

by, or probably caused by, an investigational drug.

Specifically, ***

12

Legally effective informed consent was not obtained

from a subject or the subject's legally authorized

representative, and the situation did not meet the

criteria in 21 CFR 50.23 - 50.24 for exception.

Specifically, ***

9

The IRB allowed a member to participate in the

IRB's [initial] [continuing review] of a project in which

the member had a conflicting interest. Specifically,

***

9

The IRB [has no] [did not follow] written procedures

for ensuring prompt reporting to [the IRB]

[appropriate institutional officials] [the FDA] of any

instance of serious or continuing noncompliance

with theses regulations or the requirements or

determinations of the IRB. Specifically, ***

9

There was no statement in the informed consent

document that [described the extent, if any, to which

confidentiality of records identifying the subject

would be maintained] [noted the possibility that the

Food and Drug Administration might inspect the

records]. Specifically, ***

9

Page 35

BIMO




unanticipated problems involving risks to human

subjects or others. Specifically, ***

8

The IRB does not conduct continuing review of

research at intervals [appropriate to the degree of

risk] [of not less than once per year]. Specifically,

***

8




suspension or termination of IRB approval .

Specifically, ***

8

Failure to ensure that an investigation was

conducted in accordance with the general

investigational plan and protocols as specified in the

IND. Specifically, ***

8

The IRB used an expedited review procedure for

research which did not appear in an FDA list of

categories eligible for expedited review, and which

had not previously been approved by the IRB [within

one year]. Specifically, ***

8

Failure to obtain [an] [a complete] investigator

statement, form FDA-1572, before permitting an

investigator to participate in an investigation.

Specifically, ***

7

Failure to assure that an IRB [complying with

applicable regulatory requirements] was responsible

for the initial and continuing review and approval of a

clinical study. Specifically, ***

7

The informed consent document lacked an

explanation of whom to contact [for answers to

pertinent questions about the research and research

subjects' rights] [in the event of a research-related

injury to the subject]. Specifically, ***

6

The informed consent document did not contain [a

description of the procedures to be followed]

[identification of any procedures which were

experimental]. Specifically, ***

5

The IRB does not include at least one member who

is not otherwise affiliated with the institution, and

who is not part of the immediate family of a person

who is affiliated with the institution. Specifically, ***

5


procedure for determining which projects [require

review more often than annually] [need verification

from sources other than the investigator that no

material changes have occurred since previous IRB

review] . Specifically, ***

5

Page 36

BIMO

Lack of [adequate] records covering [receipt]

[shipment to investigators] [disposition] of an

investigational drug. Specifically, ***

5

The study director failed to assure that all raw data,

documentation, protocols, specimens, and final

reports were transferred to the archives during or at

the close of the study. Specifically, ***

4

Not all nonclinical laboratory studies were conducted

in

accordance with the protocol. Specifically, ***

4

The final study report did not include a description of

all circumstances that may have affected the quality

or integrity of the data. Specifically, ***

4

Copies have not been maintained of all

correspondence between the IRB and the

investigators. Specifically, ***

4

A clinical investigator did not report to the IRB [,

within five days of use,] the emergency use of a test

article for which the IRB had not reviewed the

research proposal. Specifically, ***

4

The IRB did not determine [at the time of initial

review] [at the time of continuing review for an on-

going study which was started on/before April 30,

2001] that a study was in compliance with 21 CFR

Part 50 Subpart D, "Additional Safeguards for

Children in Clinical Investigations." Specifically, ***

4


procedure for reporting its [findings] [actions] to the

[investigator] [institution]. Specifically, ***

4

The general requirements for informed consent were

not met in that the information given was not in

language understandable to the subject or the

subject's representative. Specifically, ***

4

The study director failed to assure that unforeseen

circumstances that might affect the quality and

integrity of the nonclinical laboratory study were

noted when they occurred and corrective action was

taken and documented. Specifically, ***

3

The quality assurance unit failed to maintain a copy

of a master schedule sheet that contained all

required elements for all nonclinical laboratory

studies conducted by the testing facility.

Specifically, ***

3

Page 37

BIMO

The quality assurance unit failed to review the final

study report to assure that such report accurately

described the methods and standard operating

procedures, and that the reported results accurately

reflected the raw data of the study. Specifically, ***

3

Procedures have not been established for the

handling of the test and control articles to ensure

that [there is proper storage] [distribution is made in

a manner designed to preclude the possibility of

contamination, deterioration, or damage] [proper

identification is maintained throughout the

distribution process] [the receipt and distribution of

each batch is documented including the date and

quantity of each batch distributed or returned].

Specifically, ***

3

Not all changes in, or revisions of, an approved

protocol and the reasons therefore were

documented, signed by the study director, dated,

and maintained with the protocol. Specifically, ***

3

The IRB used an expedited review procedure to

review supposedly minor changes to previously-

approved research, but the changes were not minor

in nature. Specifically, ***

3

Records have not been [prepared] [maintained] of all

continuing review activities. Specifically, ***

3

Records required by 21 CFR 56 have not been

maintained for three years following completion of

the research. Specifically, ***

3


procedure for ensuring that changes in approved

research, during the periods for which IRB approval

had already been given, would not be initiated

without IRB review and approval (except where

necessary to eliminate apparent immediate hazards

to the human subjects). Specifically, ***

3


procedure for ensuring prompt reporting to the IRB

of changes in research activity. Specifically, ***

3

The informed consent document lacked a

description of reasonably foreseeable risks or

discomforts to the subject. Specifically, ***

3

There was [no] [an incomplete] disclosure in the

informed consent document of appropriate alternate

procedures or courses of treatment, if any, that

might be advantageous to the subject. Specifically,

***

3

Page 38

BIMO

The informed consent document did not contain a

statement that [participation was voluntary] [refusal

to participate would involve no penalty or loss of

benefits to which the subject was otherwise entitled]

[the subject might discontinue participation at any

time without penalty or loss of benefits to which the

subject was otherwise entitled]. Specifically, ***

3

The informed consent document did not include a

statement that significant new findings developed

during the course of the research, which might relate

to the subject's willingness to continue participation,

would be provided to the subject. Specifically, ***

3

Testing facility management failed to designate a

study director before each study was initiated.

Specifically, ***

2

The study director failed to assure that the protocol,

including any change, was approved and was

followed. Specifically, ***

2

The study director failed to assure that all

experimental data, including observations of

unanticipated responses of the test system, were

accurately recorded and verified. Specifically, ***

2

The study director failed to assure that all applicable

GLP regulations were followed. Specifically, ***

2

Not all [equipment used in the generation,

measurement, or assessment of data] [equipment

used for facility environmental control] is of

appropriate design and adequate capacity to

function according to the protocol and is suitably

located for operation, inspection, cleaning, and

maintenance. Specifically, ***

2

Not all equipment used for the generation,

measurement, or assessment of data is adequately

tested, calibrated and/or standardized. Specifically,

***

2

Not all deviations from standard operating

procedures in a study were authorized by the study

director and documented in the raw data.

Specifically, ***

2

Not all significant changes in established standard

operating procedures were properly authorized in

writing by management. Specifically, ***

2

Page 39

BIMO

Standard operating procedures have not been

established for [animal room preparation] [animal

care] [receipt, identification, storage, handling,

mixing, and method of sampling of the test and

control articles] [test system observations]

[laboratory tests] [handling of animals found

moribund or dead during study] [necropsy of animals

or postmortem examination of animals] [collection

and identification of specimens] [histopathology]

[data handling, storage, and retrieval] [maintenance

and calibration of equipment] [transfer, proper

placement, and identification of animals].

Specifically, ***

2

A final report was not prepared for each nonclinical

laboratory study. Specifically, ***

2

The IRB is not composed of at least five members

[with varying backgrounds to promote complete and

adequate review of research activities commonly

conducted by the institution]. Specifically, ***

2

The IRB invited an individual with competence in a

special area to assist in the review of complex

issues which required expertise beyond or in

addition to that available on the IRB; however, the

IRB allowed the individual to vote with the IRB.

Specifically, ***

2

The IRB does not require that information given to

subjects as part of informed consent contain all

necessary elements of informed consent.

Specifically, ***:

2

Copies have not been [prepared] [maintained] of all

[research proposals reviewed] [scientific evaluations,

if any, accompanying research proposals] [approved

sample consent documents] [progress reports

submitted by investigators] [reports of injuries to

subjects]. Specifically, ***

2

The IRB approved a clinical investigation in which

more than minimal risk to children was presented by

1) an intervention or procedure that held out the

prospect of direct benefit for the individual subjects,

and/or 2) by a monitoring procedure which was likely

to contribute to the individual subjects' well-being.

However, the IRB did not [find] [document] that [the

risk was justified by the anticipated benefit to the

subjects] [the relation of the anticipated benefit to

the risk was at least as favorable to the subjects as

that presented by available alternative approaches]

[adequate provisions had been made for soliciting

the assent of the children and the permission of their

parents or guardians, as set forth in 21 CFR 50.55].

Specifically, ***

2

Page 40

BIMO

Permission by parents or guardians for the

participation of children as subjects in a clinical

investigation was not documented in accordance

with and to the extent required by 21 CFR 50.27.

Specifically, ***

2

The IRB approved the conduct of research involving

children as subjects, but did not determine that the

research was in compliance with 21 CFR 50 Subpart

D. Specifically, ***

2

The informed consent document did not contain a

statement that the test article or procedure might

involve risks to the subject (or to the embryo or

fetus, if the subject is or may become pregnant) that

are currently unforeseeable. Specifically, ***

2

The informed consent document did not contain [a

statement that the study involved research] [an

explanation of the purposes of the research, and the

expected duration of the subject's participation].

Specifically, ***

2

The IRB does not review all research activities

covered by the regulations. Specifically, ***

2

Failure to monitor the progress of an investigation

conducted under your IND. Specifically, ***

2

Failure to maintain [adequate] written records of the

disposition of an investigational drug in accordance

with 21 CFR Part 312.57. Specifically, ***

2

Unused supplies of an investigational drug were not

[returned to the sponsor] [disposed of in accordance

with sponsor instructions]. Specifically, ***

2

Investigational records were not retained for a period

of two years following [approval of a drug's

marketing application] [discontinuance of the

investigation and notification of FDA]. Specifically,

***

2

A study drug was [administered to subjects]

[provided to persons] not under the investigator's

personal supervision or under the supervision of a

subinvestigator responsible to the investigator.

Specifically, ***

2

For other than expedited reviews, research

approved by the IRB does not always receive the

approval of a majority of those IRB members

present. Specifically, ***

2

Page 41

BIMO

The general requirements for informed consent were

not met in that [you] [the investigator] did not seek

consent under circumstances that [provided the

prospective subject or the subject's representative

sufficient opportunity to consider whether or not to

participate] [minimized the possibility of coercion or

undue influence]. Specifically, ***

2

Not all consulting laboratories, contractors, or

grantees were notified that the study must be

conducted in compliance with FDA GLP regulations.

Specifically, ***

1

Not all individuals engaged in the conduct of or

responsible for the supervision of a nonclinical

laboratory study have education, training, and

experience, or combination thereof, to enable that

individual to perform assigned functions.

Specifically, ***

1

Testing facility management failed to assure that

there was a quality assurance unit in conformance

with FDA GLP regulations. Specifically, ***

1

Testing facility management failed to assure that all

personnel, resources, facilities, equipment,

materials, and methodologies were available as

scheduled. Specifically, ***

1

Testing facility management failed to assure that

any deviations from FDA GLP regulations reported

by the quality assurance unit were communicated to

the study director and corrective actions were taken

and documented. Specifically, ***

1

The quality assurance unit, for any given study, was

not entirely separate from and independent of the

personnel engaged in the direction and conduct of

that study. Specifically, ***

1

The quality assurance unit failed to determine

whether any deviations from approved protocols or

standard operating procedures had been made with

proper authorization and documentation.

Specifically, ***

1

The quality assurance unit failed to prepare and sign

a statement to be included with the final study report

which specified the dates inspections were made

and findings reported to management and to the

study director. Specifically, ***

1

The quality assurance unit failed to provide access

to the testing facility's written procedures for

inspection of nonclinical laboratory studies.

Specifically, ***

1

The testing facility does not provide appropriate

storage areas for preservation of perishable

supplies. Specifically, ***

1

Page 42

BIMO

The testing facility does not provide storage areas

for the test and control article and test and control

mixtures [separate from areas housing the test

systems] [adequate to preserve the identity,

strength, purity, and stability of the articles and

mixtures]. Specifically, ***

1

The standard operating procedures for routine

inspection, cleaning, maintenance, testing,

calibration, and/or standardization of equipment are

not adequate. Specifically, ***

1

The testing facility does not have written standard

operating procedures setting forth nonclinical

laboratory study methods that management is

satisfied are adequate to insure the quality and

integrity of the data generated in the course of a

study. Specifically, ***

1

Not all animal cages, racks and accessory

equipment were cleaned and sanitized at

appropriate intervals. Specifically, ***

1

Not all animal feed and water were analyzed

periodically to ensure that expected contaminants

were not present at levels above those specified in

the protocol. Specifically, ***

1

The identity, strength, purity, composition, or other

characteristics of each batch of test and control

article have not been appropriately defined and

documented. Specifically, ***

1

Not all protocols contained the name of the sponsor

and the name and address of the testing facility at

which the study is being conducted. Specifically, ***

1

Not all test systems were monitored in conformity

with the protocol. Specifically, ***

1

Data generated without the use of an automated

data collection system were not recorded directly,

promptly, and legibly in ink. Specifically, ***

1

Not all changes in entries were made so as not to

obscure the original entry, indicated the reason for

such change, and were dated and signed or

identified at the time of the change. Specifically, ***

1

The final study report did not include the objectives

and procedures stated in the approved protocol,

including any changes in the original protocol.

Specifically, ***

1

The final study report did not include the stability of

the test and control articles under the conditions of

administration. Specifically, ***

1

Page 43

BIMO

The final study report did not include a description of

the dosage, dosage regimen, route of

administration, and duration. Specifically, ***

1

The final study report did not include the signed and

dated reports of each of the individual scientists or

other professionals involved in the study.

Specifically, ***

1

An individual was not identified as responsible for

the archives. Specifically, ***

1

Not all material retained or referred to in the archives

was indexed to permit expedient retrieval.

Specifically, ***

1

Not all required summaries of training and

experience and job descriptions were retained for

the required period of time. Specifically, ***

1

Not all required records were retained as original

records or as true copies of the original records.

Specifically, ***

1

A clinical investigation requiring prior submission to

the FDA was initiated without [IRB review] [IRB

approval] [being subject to continuing IRB review].

Specifically, ***

1

The IRB does not include [at least one member

whose primary concerns are in the scientific area]

[at least one member whose primary concerns are in

nonscientific areas]. Specifically, ***

1

The IRB has not [promptly] provided to the sponsor

of research involving an exception to informed

consent a copy of information that has been publicly

disclosed by regulation. Specifically, ***

1

The IRB has not promptly notified in writing [the

investigator] [the institution] when the IRB has

[approved] [disapproved] [required modifications to

secure IRB approval of] proposed research activity.

Specifically, ***

1

The IRB approved the conduct of research, but did

not determine that the risks to subjects were

reasonable in relation to the anticipated benefits (if

any) to subjects, and to the importance of the

knowledge that might be expected to result.

Specifically, ***

1

The IRB approved the conduct of research, but did

not determine that informed consent would be

appropriately documented. Specifically, ***

1

Page 44

BIMO

The IRB approved the conduct of research in a

situation where some or all of the subjects were

likely to be vulnerable to coercion or undue

influence, but did not determine that additional

safeguards had been included in the study to protect

the rights and welfare of those subjects.

Specifically, ***

1

Documentation has not been [prepared]

[maintained] of all statements of significant new

findings provided to subjects, as required by 21 CFR

50.25. Specifically, ***

1

The IRB approved a study in which more than

minimal risk to children was presented by [an

intervention or procedure that did not hold out the

prospect of direct benefit for the subjects] [a

monitoring procedure that was not likely to

contribute to the well-being of the subjects].

However, the IRB did not [find] [document] that [the

risk represented a minor increase over minimal risk]

[the intervention or procedure presented

experiences to subjects that were reasonably

commensurate with those inherent in their actual or

expected medical, dental, psychological, social, or

educational situations] [the intervention or procedure

was likely to yield generalizable knowledge about

the subjects' disorder or condition that was of vital

importance for the understanding or amelioration of

the subjects' disorder or condition] [adequate

provisions had been made for soliciting the assent of

the children and permission of their parents or

guardians]. Specifically, ***

1

The IRB waived the requirement for a written

consent form signed by the [subject] [subject's

legally authorized representative], without first

determining that the requirements in 21 CFR 50.24

for an exception from informed consent for

emergency research were met. Specifically, ***

1

A description of any benefits [to the subject] [to

others] which might reasonably be expected from

the research was not included in the informed

consent document. Specifically, ***

1

In approving an investigation without requiring

informed consent, the IRB did not [find] [document]

that obtaining informed consent was not feasible.

Specifically,***

1

Page 45

BIMO



that participation in the research held out the

prospect of direct benefit to the subjects because

[they faced a life-threatening situation requiring

intervention] [evidence from preclinical studies

supported the potential for intervention to provide a

direct benefit to subjects] [associated risks were

reasonable under the circumstances].

Specifically,***

1



that appropriate informed consent procedures and

an informed consent document consistent with 21

CFR 50.25 were in place for use [with subjects or

their legally authorized representatives in situations

where use of such procedures and documents was

feasible] [when providing an opportunity for a family

member to object to a subject's participation in the

clinical investigation]. Specifically,***

1



that additional protections of the rights and welfare

of the subjects would be provided, including

[consultation with, and public disclosure to, the

communities in which the clinical investigation would

be conducted, and from which the subjects would be

drawn] [establishment of an independent data

monitoring committee to exercise oversight of the

clinical investigation] [attempting to contact (within

the therapeutic window, when obtaining informed

consent was not feasible and a legally authorized

representative was not reasonably available) the

subject's family member who was not a legally

authorized representative, and asking whether he or

she objected to the subject's participation in the

clinical investigation]. Specifically,***

1

Investigators who were not qualified by training and

experience as appropriate experts were selected to

investigate a drug. Specifically, ***

1

Failure to obtain a curriculum vitae or other

statement of the qualifications of the investigator,

before permitting an investigator to participate in an

investigation. Specifically, ***

1

Failure to provide [FDA] [all participating

investigators] with [a] [an adequate] written IND

safety report. Specifically, ***

1

Page 46

BIMO

An investigator who did not comply with [the signed

agreement] [the general investigational plan]

[applicable regulatory requirements] was not

[promptly brought into compliance] [terminated].

Specifically, ***

1

Transfer of obligations to a contract research

organization [was not described in writing] [did not

describe each of the obligations assumed by the

contract research organization, where not all

obligations were assumed]. Specifically, ***

1

An adequate final report was not provided to the

sponsor shortly after completion of the investigator's

participation in the investigation. Specifically, ***

1

Failure to permit an authorized officer or employee

of FDA to [have access to] [copy] [verify] records or

reports. Specifically, ***

1

Failure to assure that foreign clinical research was

conducted in accordance with [the ethical principles

stated in the ``Declaration of Helsinki''] [the laws and

regulations of the country in which the research was

conducted]. Specifically, ***

1

Monitors not qualified by experience and training

were selected to monitor the progress of a clinical

investigation. Specifically, ***

1

Failure to notify FDA of the ending, for cause, of an

investigator's participation in an investigation.

Specifically, ***

1

Records and reports were not retained for two years

after [marketing application approval]

[discontinuance of the investigation and notification

of FDA]. Specifically***

1

Failure to submit to FDA [within 60 days of the

anniversary date that the IND went into effect] an

annual report of the investigation. Specifically, ***

1

Failure to obtain from an investigator a commitment

to update financial information, to allow complete

and accurate certification or disclosure statements.

Specifically, ***

1

The sponsor failed to submit an IND to the FDA prior

to conducting a clinical investigation with an

investigational new drug. Specifically,***

1

Page 47

BIMO

The IRB's [suspension] [termination of approval] for

research was not reported [promptly] to [the

investigator] [appropriate institutional officials] [the

Food and Drug Administration]. Specifically, ***

1



that [the human subjects were in a life-threatening

situation] [available treatments were unproven or

unsatisfactory] [the collection of valid scientific

evidence was necessary to determine the safety and

effectiveness of particular interventions].

Specifically, ***

1

An individual authorized to act on behalf of an IRB

which reviews clinical investigations that are

intended to support applications for research or

marketing permits for FDA-regulated products has

not submitted registration information. Specifically,

***

1

Page 48

Devices


Devices 630 21 CFR 803.17 Lack of Written MDR Procedures

3130 21 CFR 820.100(a) Lack of or inadequate procedures

3696 21 CFR 820.100(b) Documentation

546 21 CFR 820.75(a) Lack of or inadequate process validation

4189 21 CFR 820.198(a) General

479 21 CFR 820.50 Purchasing controls, Lack of or inadequate

procedures

14713 21 CFR 820.198(a) Lack of or inadequate complaint procedures

3172 21 CFR 820.198(c) Investigation of device failures

2327 21 CFR 820.22 Quality audits - Lack of or inadequate

procedures

3415 21 CFR 820.22 Quality Audit/Reaudit - conducted

3103 21 CFR 820.30(i) Design changes - Lack of or Inadequate

Procedures

731 21 CFR 803.50(a)(1) Report of Death or Serious Injury

2371 21 CFR 820.30(a) Design control - no procedures

732 21 CFR 803.50(a)(2) Report of Malfunction

3118 21 CFR 820.75(a) Documentation

447 21 CFR 820.40 Lack of procedures, or not maintained

3125 21 CFR 820.80(d) Lack of or inadequate final acceptance

procedures

3282 21 CFR 820.90(a) Nonconforming product, Lack of or inadequate

procedures

486 21 CFR 820.50(a) Evaluation of suppliers, contractors, etc.,

requirements

Page 49

Devices

3160 21 CFR 820.184 Lack of or inadequate DHR procedures

3666 21 CFR 820.20(c) Management review - Lack of or inadequate

procedures

3371 21 CFR 820.198(a)(3) Processing MDRs {see also 803, 804}

2974 21 CFR 812.110(b) Investigator non-compliance with

agreement/plan/regulations

3233 21 CFR 820.72(a) Calibration, Inspection, etc. Procedures Lack of

or Inadequ

3159 21 CFR 820.184 DHR content

3678 21 CFR 820.30(g) Design Validation - Risk analysis not

performed/inadequate

2350 21 CFR 820.25(b) Training - Lack of or inadequate procedures

3669 21 CFR 820.20(c) Management review - defined interval, sufficient

frequency

541 21 CFR 820.70(c) Environmental control Lack of or inadequate

procedures

3837 21 CFR 820.25(b) Training records

3104 21 CFR 820.30(j) Design history file

2302 21 CFR 820.20(e) Quality System Procedures

3120 21 CFR 820.80(a) Lack of or inadequate procedures - Acceptance

activities

3121 21 CFR 820.80(b) Lack of or inadequate receiving acceptance

procedures

2968 21 CFR 812.100 Investigator non-compliance with

agreement/plan/regulations

3291 21 CFR 820.100(b) Procedures

3369 21 CFR 820.198(a)(1) Uniform and timely processing

3692 21 CFR 820.100(a)(4) CAPA verification/validation of

corrective/preventive action

14505 21 CFR 812.140(a)(3) Investigator's subject records inadequate

Page 50

Devices

4059 21 CFR 820.22 Quality Audits - defined intervals

3690 21 CFR 820.100(a)(3) Identification of actions needed

3128 21 CFR 820.90(a) Nonconforming product control

3680 21 CFR 820.70(a) Process control procedures, Lack of or

inadequate procedures

419 21 CFR 820.20(b) Lack of or inadequate organizational structure

3101 21 CFR 820.30(g) Design validation- Lack of or inadequate

procedures

3331 21 CFR 820.181(e) DMR - not or inadequately maintained

3331 21 CFR 820.181 DMR - not or inadequately maintained

4191 21 CFR 806.10(a)(1) Report of risk to health

538 21 CFR 820.70(a) Process control procedures

3127 21 CFR 820.80(e) Documentation

3201 21 CFR 820.40(a) Not approved or obsolete document retrieval

537 21 CFR 820.70(a) Production processes

2650 21 CFR 820.30(f) Design verification - Lack of or inadequate

procedures

3164 21 CFR 820.184(d) Acceptance records

3301 21 CFR 820.100(a)(2) Investigation procedures

3167 21 CFR 820.198(a) Complete files maintained

631 21 CFR 803.17(a)(1) Lack of System for Event Evaluations

Page 51

Devices

3299 21 CFR 820.100(a)(1) Procedure for analysis of data sources

3192 21 CFR 820.30(g) Design validation - user needs and intended

uses

3263 21 CFR 820.250(b) Sampling plans

3665 21 CFR 820.20(b)(3) Management representative

14722 21 CFR 820.40 Procedures not adequately established or

maintained

3687 21 CFR 820.100(a)(1) Analysis of data sources

3102 21 CFR 820.30(h) Design transfer - Lack of or inadequate

procedures

3108 21 CFR 820.70(e) Contamination control, Lack of or inadequate

procedures

3132 21 CFR 820.120 Lack of or inadequate procedures for labeling

3119 21 CFR 820.75(b) Lack/Inad procedure-Monitoring/Control of

Validated Proces

3155 21 CFR 820.181(a) DMR device specifications

3235 21 CFR 820.72(a) Equipment control activity documentation

3250 21 CFR 820.72(b)(2) Calibration documentation

3285 21 CFR 820.90(b)(2) Product rework procedures, Lack of or

inadequate procedures

3206 21 CFR 820.50(b) Approval, inadequate purchasing data

3426 21 CFR 820.50(a)(1) Documented evaluation

3286 21 CFR 820.90(b)(1) Procedures for product review,disposition lack

of/inadequate

4057 21 CFR 820.20(a) Management ensuring quality policy is

understood

2269 21 CFR 820.20(a) Quality policy and objectives

2604 21 CFR 820.30(e) Design review - Lack of or inadequate

procedures

Page 52

Devices

539 21 CFR 820.70(b) Production and Process Change Procedures,

lack of or Inad.

454 21 CFR 820.40(a) Document review, approval by designated

individual

2293 21 CFR 820.20(d) Quality plan

3168 21 CFR 820.198(a) Complaints

3380 21 CFR 820.198(e)(6) Results of investigation

3427 21 CFR 820.50(a)(2) Supplier oversight

14712 21 CFR 820.184 DHR - not or inadequately maintained

632 21 CFR 803.17(a)(2) Lack of System for Determining MDR Events

2928 21 CFR 812.40 Sponsors' general responsibilities

2328 21 CFR 820.22 Quality audits - auditor independence

3226 21 CFR 820.70(g)(1) Maintenance schedule, Lack of or inadequate

schedule

3284 21 CFR 820.90(a) Nonconforming product evaluation/investigation

2970 21 CFR 812.100 Investigator lack of informed consent

3688 21 CFR 820.100(a)(1) Analysis of data/reports from data sources

2351 21 CFR 820.25(b) Training

3170 21 CFR 820.198(b) Review and evaluation for investigation

3303 21 CFR 820.100(a)(4) Verify, validate change {see also 820.100(a)}

3433 21 CFR 820.75(c) Process changes - review, evaluation and

revalidation

3332 21 CFR 820.184(e) ID label, labeling

3686 21 CFR 820.90(b)(2) Product rework documentation, DHR {see also

820.184}

Page 53

Devices

4058 21 CFR 820.20 Management responsibility

6800 21 CFR 807.20 Establishment not registered

3117 21 CFR 820.70(i) Software validation for automated processes

3171 21 CFR 820.198(b) Rationale documented for no investigation

3268 21 CFR 820.80(b) Incoming inspection, testing, verification

3270 21 CFR 820.80(c) Documentation

3203 21 CFR 820.40(b) Document change records, maintained.

3288 21 CFR 820.90(b)(1) Documentation of disposition, justification,

signature

3434 21 CFR 820.75(c) Documentation - review in response to changes

or deviations

3671 21 CFR 820.25(a) Personnel

3676 21 CFR 820.30(f) Design verification - documentation

3345 21 CFR 820.200(a) Servicing - Lack of or inadequate procedures

3375 21 CFR 820.198(e) Records of complaint investigation

2985 21 CFR 812.140(a)(3)(ii) Investigator records of relevant observations

inadequate

4212 21 CFR 806.20(b)(4) Justification for not reporting

502 21 CFR 820.60 Identification procedures, Lack of or inadequate

procedures

2557 21 CFR 820.30(c) Design input - documentation

2630 21 CFR 820.30(e) Design review - documentation

3157 21 CFR 820.181(c) DMR QA procedures and specifications

Page 54

Devices

3231 21 CFR 820.70(i) Documentation of software validation

3232 21 CFR 820.72(a) Equipment suitability & capability

3379 21 CFR 820.198(e)(5) Nature and details of complaint

4070 21 CFR 820.30(g) Design validation - documentation

3425 21 CFR 820.50(a)(1) Evaluation and Selection, Suppliers,

Contractors, etc.

812 21 CFR 803.56 Submission Within One Month

3021 21 CFR 812.150(a)(1) Investigator report of unanticipated adverse

effects

3689 21 CFR 820.100(a)(2) Investigation

4193 21 CFR 806.10(b) Time to report - 10 days

2430 21 CFR 820.30(b) Design plans - Lack of or inadequate

3262 21 CFR 820.250(a) Statistical techniques - Lack of or inadequate

procedures

3677 21 CFR 820.30(g) Design validation - software validation not

performed

14716 21 CFR 820.30(f) Design verification - output does not meet input

requirement

2984 21 CFR 812.140(a)(3)(i) Investigator records of informed consent

inadequate

3302 21 CFR 820.100(a)(3) Identifying corrective & preventive actions

7013 21 CFR 812.110(d) Inadequate financial disclosure by investigator

14507 21 CFR 812.140(a)(3)(ii) Investigator adverse effect records inadequate

2279 21 CFR 820.20(b)(2) Resources

Page 55

Devices

3123 21 CFR 820.80(c) Lack of or inadequate In-process acceptance

procedures

3139 21 CFR 820.140 Lack of or inadequate procedures for handling

3199 21 CFR 820.40(a) Document review, approval documentation

3283 21 CFR 820.90(a) Specific non-conforming product procedures

3432 21 CFR 820.75(b)(2) Documentation of validated process

performance

3328 21 CFR 820.180(b) Retention period

14720 21 CFR 820.50(a)(3) Acceptable supplier records, inadequate

records

3683 21 CFR 820.70(g) Equipment Installation, Placement, Specified

Requirements

2981 21 CFR 812.140(a)(2)(i) Investigator device accountability inadequate

3309 21 CFR 820.120(b) Examination for accuracy

4208 21 CFR 806.20(a) Records not kept

6802 21 CFR 807.21(a) Annual registration

6803 21 CFR 807.20(a) Devices not listed

2330 21 CFR 820.22 Quality audit corrective action, reaudits {see

also 820.100}

2601 21 CFR 820.30(d) Essential design outputs

2648 21 CFR 820.30(f) Design verification procedures

3111 21 CFR 820.70(f) Buildings

3144 21 CFR 820.160(a) Control/distribution procedures

Page 56

Devices

3173 21 CFR 820.198(d) Evaluation, timeliness, identification

3191 21 CFR 820.30(g) Design validation - production units

3207 21 CFR 820.50(b) Supplier notification of changes

3149 21 CFR 820.180 Availability

3227 21 CFR 820.70(g)(1) Activity documentation

3204 21 CFR 820.40(b) Change records, content

3396 21 CFR 820.80(d)(1) DMR required activities {see also 820.181}

3414 21 CFR 820.200(d)(6) Test and inspection data

3416 21 CFR 820.70(a)(1) Process control instructions

3428 21 CFR 820.50(a)(3) Acceptable supplier records

3667 21 CFR 820.20(c) Management review accomplishment

3333 21 CFR 820.184(f) Device identification, control numbers

3370 21 CFR 820.198(a)(2) Oral complaints

633 21 CFR 803.17(a)(3) Lack of System for Timely Submission of

Reports

635 21 CFR 803.17(b)(1) Info evaluated to determine if event was

reportable

778 21 CFR 803.52(f)(1) Type of Reportable Event

Page 57

Devices

2980 21 CFR 812.140(a)(1) Investigator correspondence records

inadequate

3304 21 CFR 820.100(a)(5) Changes to correct/prevent quality problems

7012 21 CFR 812.100 Investigator lack of control of investigational

devices

2429 21 CFR 820.30(b) Establish the design and development plan

2470 21 CFR 820.30(c) Design input procedures - appropriateness

3141 21 CFR 820.150(a) Storage procedures to prevent mix-ups

3142 21 CFR 820.150(a) Storage procedures to avoid release of

unsuitable product

3162 21 CFR 820.184(b) Quantity manufactured

3198 21 CFR 820.40(b) Document changes, review and approval,

communication

3224 21 CFR 820.70(g)(2) Periodic equipment inspection lack of or

inadequate procedu

3236 21 CFR 820.72(b) Calibration procedures - content

3269 21 CFR 820.80(b) Incoming acceptance records, documentation

3397 21 CFR 820.80(d)(2) Review of data and documentation

3841 21 CFR 820.90(b)(2) Product rework adverse effects {see also

820.184}

14718 21 CFR 820.30(g) Design validation - Risk analysis

3682 21 CFR 820.70(d) Implementing Personnel Procedures, Health,

Cleanliness.

636 21 CFR 803.17(b)(2) Reports and information documentation

738 21 CFR 803.52(a)(1) Patient Name or Other Identifier

2916 21 CFR 812.7(d) Investigational device represented as safe and

/or effective

Page 58

Devices

2973 21 CFR 812.110(a) Subject participation prior to study approval

2991 21 CFR 812.140(b)(1) Sponsor correspondence records inadequate

3190 21 CFR 820.30(g) Design validation acceptance criteria

3300 21 CFR 820.100(a)(1) Statistical methodology

3693 21 CFR 82

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